Lung Non-Small Cell CarcinomaPhase 1/2NCT05501665
Split Course Adaptive Radiation Therapy With Pembrolizumab With/Without Chemotherapy for Treating Stage IV Lung Cancer
A Phase 1/2 study testing Biospecimen Collection, Carboplatin and Computed Tomography in people with Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage III Lung Cancer
- What is being tested?
- Biospecimen Collection, Carboplatin and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 9 May 2023to 1 Feb 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years at time of informed consent
- • Histologically documented or cytologically confirmed diagnosis of stage IVA or IVB (M1b or M1c) or locally advanced (not eligible for standard of care [SOC] chemoradiation) non-small cell lung cancer with evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria
- Available tumor material (< 6 months old) adequate for confirmation of programmed cell death 1 ligand 1 (PD-L1) expression per local standard of care testing
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate organ function to receive therapy as determined by investigators and other treating physicians
- Participants with brain metastases that can be comprehensively managed with surgery and/or stereotactic radiosurgery, prior to initiation of chemo-immunotherapy are allowed. Number of brain metastases allowed is not specified at eligibility is at discretion of investigator
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- Contraceptive use should be initiated or continued per guidance in labeling for approved chemotherapies
- Female patients must be non-pregnant and not breastfeeding.
- If woman of childbearing potential (WOCBP), must utilize highly effective contraceptive method (failure rate of < 1% per year) throughout intervention period and continued per guidance specified in labeling for approved chemotherapies. Must have negative pregnancy test (serum or urine) within 1 week prior to initiation of first cycle of therapy
- Eligible for immunotherapy-based systemic regimens per judgment of patient's study physician
- Able to submit written informed consent
Who cannot join
- Mixed small cell histology
- Confirmed candidate (per study physician) for alternative systemic therapy if preferred by treating physician (i.e. mEGFR, ALK, KRAS G12C or ROS1 mutations). Testing not required for enrollment
- Brain metastases that would require administration of whole brain radiotherapy for management on required screening brain MRI within 21 days of day 1 of study treatment
- Symptomatic malignant ascites or malignant pleural effusion (sampling not required). Pleural metastases are allowed if deemed targetable with radiotherapy
- Major surgery (requiring general anesthesia or at discretion of study physician) within 4 weeks prior to study enrollment that would prevent treatment with SiCARIO regimen
- History of organ transplant requiring therapeutic immunosuppression
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- Known clinically significant (per study physician) acute or chronic infections including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or active tuberculosis (testing not required). Patients with HBV and HCV must be on stable dose of antiviral therapy on study entry
- Uncontrolled intercurrent illness including, but not limited to, New York Heart Association (NYHA) class III-IV congestive heart failure, uncontrolled hypertension (average systolic blood pressure greater than or equal to 140 or average diastolic blood pressure greater than or equal to 90 despite optimal medical therapy), unstable angina pectoris, cardiac arrythmia, active peptic ulcer disease, bleeding diatheses or psychiatric illness that would limit in the judgment of the study physician
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of day 1 of study treatment
- History of prior independent malignancy within 3 years of enrollment, except for adequately treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma in situ (e.g. cervix or non-invasive bladder cancer)
- Receipt of prior >1 cycle of immune checkpoint inhibitor for current malignancy (prior cytotoxic chemotherapy is allowed)
- Prior radiotherapy that would preclude delivery of protocol- based radiotherapy to normal organ tolerance per patient's study physician
- Current or prior use of immunosuppressive medications within 28 days of enrollment with exception of intranasal or inhaled corticosteroids or systemic steroids at physiologic doses (equivalent to less than or equal to 10 mg/day of prednisone). Systemic steroids required during therapy for adverse event (AE) management and for residual neurologic complications from management of central nervous system (CNS) metastases are allowed at doses exceeding 10 mg/day of prednisone equivalents
- Active autoimmune disease requiring systemic treatment within past 1 year
- Receipt of live attenuated vaccine within 30 days of enrollment
- Use of prohibited concomitant drug within 30 days of enrollment
- Known severe (>= grade 3 Common Terminology Criteria for Adverse Events [CTCAE]) hypersensitivity to study intervention or formulation
- Concurrent enrollment in another clinical trial (unless observational or within follow-up period)
- Any condition at discretion of investigator that will preclude participation in the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Vanderbilt-Ingram Service for Timely Access, 800-811-8480, cip@vumc.org
Evan Osmundson, MD, PhD
About this study
Official title: SiCARIO (Split Course Adaptive Radioimmunotherapy) for the Treatment of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Using Biologically-Adaptive Radiotherapy - A Phase I/II Study
This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab, cemiplimab, atezolizumab or nivolumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs like carboplatin, pemetrexed, and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety of adaptive split course hypo-fractionated radiation therapy (RT) with immunotherapy containing systemic regimens.
II. Evaluate efficacy of the use of adaptive split course hypo-fractionated RT with immunotherapy containing systemic regimens.
SECONDARY OBJECTIVES:
- Evaluate progression and survival benefit of split course adaptive radioimmunotherapy (SiCARIO) regimen.
II. Identify potential functional radiomic biomarkers of response to SiCARIO regimen.
III. Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive RT.
OUTLINE:
PRIMARY OBJECTIVES:
- Evaluate the safety of adaptive split course hypo-fractionated radiation therapy (RT) with immunotherapy containing systemic regimens.
II. Evaluate efficacy of the use of adaptive split course hypo-fractionated RT with immunotherapy containing systemic regimens.
SECONDARY OBJECTIVES:
- Evaluate progression and survival benefit of split course adaptive radioimmunotherapy (SiCARIO) regimen.
II. Identify potential functional radiomic biomarkers of response to SiCARIO regimen.
III. Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive RT.
OUTLINE:
Patients are assigned to 1 of 11 standard treatment regimens, in combination with radiation therapy, as determined by the tumor histology and PD-L1 status.
Patients with non-squamous histology and any PD-L1 status are assigned to arms 1-4.
ARM I: Patients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM II: Patients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM III: Patients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM IV: Patients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
Patients with squamous histology and any PD-L1 histology are assigned to arms 5-7
ARM V: Patients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
ARM VI: Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
ARM VII: Patients receive carboplatin, paclitaxel and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
Patients with PD-L1 ≥ 50% are assigned to arms 8-10
ARM VIII: Patients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM IX: Patients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM X: Patients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
Patients with any PD-L1 status or histology who are not a chemotherapy candidate are assigned to arm 11
ARM XI: Patients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
After completion of study treatment, patients are followed up at 4 weeks, 12 weeks, and then every 12 weeks for 2 years.
- Being tested
- Biospecimen Collection, Carboplatin, Computed Tomography, Fludeoxyglucose F-18, Nab-paclitaxel
- Keywords
- Oligometastasis, Adaptive Radiotherapy, Immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Correlative studies
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given carboplatin
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo PET/CT
Fludeoxyglucose F-18Other
Also called 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18
Given IV
Nab-paclitaxelDrug
Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel
Given nab-paclitaxel
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given pembrolizumab
PemetrexedDrug
Also called MTA, Multitargeted Antifolate, Pemfexy
Given pemetrexed
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan
Undergo PET/CT
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo radiation therapy
[18-F] (fluoropropyl)-L-glutamate (FSPG) PET scanOther
Undergo PET scan
IpilimumabBiological
Given Ipilimumab
NivolumabBiological
Given Nivolumab
CemiplimabBiological
Given Cemiplimab
AtezolizumabBiological
Given Atezolizumab
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation) | Experimental | Patients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Biological: Pembrolizumab; Drug: Pemetrexed; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan |
| Arm II (carboplatin, pemetrexed, cemiplimab, radiation) | Experimental | Patients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Drug: Pemetrexed; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Cemiplimab |
| Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation) | Experimental | Patients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Drug: Nab-paclitaxel; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Cemiplimab |
| Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation) | Experimental | Patients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Drug: Pemetrexed; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Ipilimumab; Biological: Nivolumab |
| Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation) | Experimental | Patients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Drug: Nab-paclitaxel; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan |
| Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation) | Experimental | Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Drug: Nab-paclitaxel; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Cemiplimab |
| Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation) | Experimental | Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Drug: Nab-paclitaxel; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Ipilimumab; Biological: Nivolumab |
| Arm VIII (pembrolizumab, radiation) | Experimental | Patients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan |
| Arm IX (atezolizumab, radiation) | Experimental | Patients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Atezolizumab |
| Arm X (cemiplimab-rwlc, radiation) | Experimental | Patients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Cemiplimab |
| Arm XI (nivolumab, ipilumumab, radiation) | Experimental | Patients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan; Biological: Ipilimumab; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Safety endpoints will be tabulated using descriptive statistics, and by appropriate subgroups. The incidence of adverse events will be summarized according to organ system in terms of severity by Common Terminology Criteria for Adverse Events and relationship to treatment
Measured: Up to 2 years
Best overall response rate
By Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Exact binomial test and 95% confidence interval (CI) will be used.
Measured: Within 6 months
Secondary outcomes (4)
Progression free survival (PFS)
Estimation of the treatment effect by a Cox proportional hazards model (stratified by chemotherapy regimen and PD-L1 expression, each stratum defines separate baseline hazard function); ties handled by replacing the proportional hazards model by the discrete logistic model; 95% CI for the hazard ratio will be calculated. Kaplan-Meier estimates and associated statistics (PFS rates at 6, 9, 12; median PFS) and corresponding 95% CI will be presented by treatment group.
Measured: Time from consent to the date of first documentation of objective progressive disease assessed by RECIST 1.1 or death, assessed at 6, 9, and 12 months
Overall survival
Estimation of the treatment effect by a Cox proportional hazards model (stratified by chemotherapy regimen and PD-L1 expression, each stratum defines separate baseline hazard function); ties handled by replacing the proportional hazards model by the discrete logistic model; 95% CI for the hazard ratio will be calculated. Kaplan-Meier estimates and associated statistics and corresponding 95% CI will be presented by treatment group.
Measured: Time from consent to the date of death due to any cause, assessed up to 2 years
New metastasis free survival
Any new lesions different from the ones present at screening are considered as new metastases.
Measured: Time from consent to the date of the first documentation of a new distant metastasis or death, assessed up to 2 years
Quantitative and qualitative markers of planning and treatment resource utilization
Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive radiation therapy (RT).
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2022
- Study start9 May 2023
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Non-Small Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Varian Medical Systems
- Responsible party
- Principal investigator, Evan Osmundson, MD, PhD, Vanderbilt-Ingram Cancer Center
- Investigators
- Evan Osmundson, MD, PhD, Principal investigator, Vanderbilt University/Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05501665
- Sponsor's protocol ID
- VICCTHOP2185
- Other IDs
- NCI-2022-05101, VICCTHOP2185, P30CA068485
- Status last verified
- Oct 2024
- First submitted
- 11 Aug 2022
- Last updated
- 17 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SiCARIO (Split Course Adaptive Radioimmunotherapy) for the Treatment of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Using Biologically-Adaptive Radiotherapy - A Phase I/II Study
- ClinicalTrials.gov ID
- NCT05501665
- Acronym / sponsor ID
- VICCTHOP2185
- Keywords
- Oligometastasis, Adaptive Radiotherapy, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Varian Medical Systems
- Study start
- 9 May 2023 (actual)
- Primary completion
- 1 Feb 2026 (estimated)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 15 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab, cemiplimab, atezolizumab or nivolumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs like carboplatin, pemetrexed, and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.
Detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety of adaptive split course hypo-fractionated radiation therapy (RT) with immunotherapy containing systemic regimens.
II. Evaluate efficacy of the use of adaptive split course hypo-fractionated RT with immunotherapy containing systemic regimens.
SECONDARY OBJECTIVES:
- Evaluate progression and survival benefit of split course adaptive radioimmunotherapy (SiCARIO) regimen.
II. Identify potential functional radiomic biomarkers of response to SiCARIO regimen.
III. Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive RT.
OUTLINE:
PRIMARY OBJECTIVES:
- Evaluate the safety of adaptive split course hypo-fractionated radiation therapy (RT) with immunotherapy containing systemic regimens.
II. Evaluate efficacy of the use of adaptive split course hypo-fractionated RT with immunotherapy containing systemic regimens.
SECONDARY OBJECTIVES:
- Evaluate progression and survival benefit of split course adaptive radioimmunotherapy (SiCARIO) regimen.
II. Identify potential functional radiomic biomarkers of response to SiCARIO regimen.
III. Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive RT.
OUTLINE:
Patients are assigned to 1 of 11 standard treatment regimens, in combination with radiation therapy, as determined by the tumor histology and PD-L1 status.
Patients with non-squamous histology and any PD-L1 status are assigned to arms 1-4.
ARM I: Patients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM II: Patients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM III: Patients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM IV: Patients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
Patients with squamous histology and any PD-L1 histology are assigned to arms 5-7
ARM V: Patients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
ARM VI: Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.
ARM VII: Patients receive carboplatin, paclitaxel and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
Patients with PD-L1 ≥ 50% are assigned to arms 8-10
ARM VIII: Patients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM IX: Patients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
ARM X: Patients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
Patients with any PD-L1 status or histology who are not a chemotherapy candidate are assigned to arm 11
ARM XI: Patients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.
All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.
After completion of study treatment, patients are followed up at 4 weeks, 12 weeks, and then every 12 weeks for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Biological: Pembrolizumab, Drug: Pemetrexed, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scanPatients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm II (carboplatin, pemetrexed, cemiplimab, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Drug: Pemetrexed, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: CemiplimabPatients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Drug: Nab-paclitaxel, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: CemiplimabPatients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Drug: Pemetrexed, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: Ipilimumab, Biological: NivolumabPatients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Drug: Nab-paclitaxel, Biological: Pembrolizumab, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scanPatients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Drug: Nab-paclitaxel, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: CemiplimabPatients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation) | Experimental | Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Drug: Nab-paclitaxel, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: Ipilimumab, Biological: NivolumabPatients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm VIII (pembrolizumab, radiation) | Experimental | Procedure: Biospecimen Collection, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Biological: Pembrolizumab, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scanPatients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm IX (atezolizumab, radiation) | Experimental | Procedure: Biospecimen Collection, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: AtezolizumabPatients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm X (cemiplimab-rwlc, radiation) | Experimental | Procedure: Biospecimen Collection, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: CemiplimabPatients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
| Arm XI (nivolumab, ipilumumab, radiation) | Experimental | Procedure: Biospecimen Collection, Procedure: Computed Tomography, Other: Fludeoxyglucose F-18, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Other: [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan, Biological: Ipilimumab, Biological: NivolumabPatients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age >= 18 years at time of informed consent
- • Histologically documented or cytologically confirmed diagnosis of stage IVA or IVB (M1b or M1c) or locally advanced (not eligible for standard of care [SOC] chemoradiation) non-small cell lung cancer with evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria
- Available tumor material (< 6 months old) adequate for confirmation of programmed cell death 1 ligand 1 (PD-L1) expression per local standard of care testing
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate organ function to receive therapy as determined by investigators and other treating physicians
Key exclusion criteria (19 listed)
- Mixed small cell histology
- Confirmed candidate (per study physician) for alternative systemic therapy if preferred by treating physician (i.e. mEGFR, ALK, KRAS G12C or ROS1 mutations). Testing not required for enrollment
- Brain metastases that would require administration of whole brain radiotherapy for management on required screening brain MRI within 21 days of day 1 of study treatment
- Symptomatic malignant ascites or malignant pleural effusion (sampling not required). Pleural metastases are allowed if deemed targetable with radiotherapy
- Major surgery (requiring general anesthesia or at discretion of study physician) within 4 weeks prior to study enrollment that would prevent treatment with SiCARIO regimen
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionCorrelative studies | Procedure or surgery | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm IX (atezolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm VIII (pembrolizumab, radiation), Arm X (cemiplimab-rwlc, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven carboplatin | Drug | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo PET/CT | Procedure or surgery | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm IX (atezolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm VIII (pembrolizumab, radiation), Arm X (cemiplimab-rwlc, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| Fludeoxyglucose F-18Also: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18Given IV | Other | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm IX (atezolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm VIII (pembrolizumab, radiation), Arm X (cemiplimab-rwlc, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| Nab-paclitaxelAlso: ABI 007, ABI-007, Abraxane, Albumin-bound PaclitaxelGiven nab-paclitaxel | Drug | Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given pembrolizumab | Biological | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VIII (pembrolizumab, radiation) |
| PemetrexedAlso: MTA, Multitargeted Antifolate, PemfexyGiven pemetrexed | Drug | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography ScanUndergo PET/CT | Procedure or surgery | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm IX (atezolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm VIII (pembrolizumab, radiation), Arm X (cemiplimab-rwlc, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| Radiation TherapyAlso: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, IrradiatedUndergo radiation therapy | Radiation | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm IX (atezolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm VIII (pembrolizumab, radiation), Arm X (cemiplimab-rwlc, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| [18-F] (fluoropropyl)-L-glutamate (FSPG) PET scanUndergo PET scan | Other | Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation), Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm IX (atezolizumab, radiation), Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm VIII (pembrolizumab, radiation), Arm X (cemiplimab-rwlc, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| IpilimumabGiven Ipilimumab | Biological | Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| NivolumabGiven Nivolumab | Biological | Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation), Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation), Arm XI (nivolumab, ipilumumab, radiation) |
| CemiplimabGiven Cemiplimab | Biological | Arm II (carboplatin, pemetrexed, cemiplimab, radiation), Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation), Arm X (cemiplimab-rwlc, radiation) |
| AtezolizumabGiven Atezolizumab | Biological | Arm IX (atezolizumab, radiation) |
Primary outcome
Incidence of adverse events
Time frame: Up to 2 years
Safety endpoints will be tabulated using descriptive statistics, and by appropriate subgroups. The incidence of adverse events will be summarized according to organ system in terms of severity by Common Terminology Criteria for Adverse Events and relationship to treatment
Best overall response rate
Time frame: Within 6 months
By Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Exact binomial test and 95% confidence interval (CI) will be used.
4 secondary outcomes
Progression free survival (PFS)
Time frame: Time from consent to the date of first documentation of objective progressive disease assessed by RECIST 1.1 or death, assessed at 6, 9, and 12 months
Overall survival
Time frame: Time from consent to the date of death due to any cause, assessed up to 2 years
New metastasis free survival
Time frame: Time from consent to the date of the first documentation of a new distant metastasis or death, assessed up to 2 years
Quantitative and qualitative markers of planning and treatment resource utilization
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Evan Osmundson, MD, PhD principal investigator
Vanderbilt University/Ingram Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Biospecimen Collection, Carboplatin and Computed Tomography in people with Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanderbilt-Ingram Service for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2024.