Non Small Cell Lung Cancer MetastaticPhase 1/2NCT03168464
Radiation and Immune Checkpoints Blockade in Metastatic NSCLC (BMS # CA209-632)
A Phase 1/2 study testing Ipilimumab, Nivolumab and Radiation therapy in people with Non Small Cell Lung Cancer Metastatic, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
NSCLC patients with metastatic disease who have failed at least one prior treatment and have a minimum of two metastatic lesions (at least one measurable), are eligible if they have an ECOG Performance Status of 0-1. Read more about this study
- Who is it for?
- Ages 19 to 90 years
- Conditions the study is for
- Non Small Cell Lung Cancer Metastatic
- What is being tested?
- Ipilimumab, Nivolumab and Radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Oct 2017to 11 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 19 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and the willingness to sign a written informed consent document;
- Histologic diagnosis of NSCLC;
- Any Kras or epidermal growth factor receptor (EGFR) status is permitted; Patients with an EGFR sensitizing mutation must have received an EGFR tyrosine kinase inhibitor (either erlotinib, gefitinib or afatinib) and patients with anaplastic lymphoma kinase (ALK) translocation must have received anti-ALK therapy.
- Patients must have at least two distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter. Patients may have additional non-measurable metastatic lesions (e.g., bone metastases);
- Patients must have prior treatment with at least one line of therapy for metastatic NSCLC. Any prior therapy is permitted except prior therapy with ipilimumab, other anti cytotoxic T-lymphocyte-associated protein (CTLA) agents or Checkpoint inhibitors;
- An interval of 2 weeks from last previous therapy is required;
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- Patients must have recovered from the toxic effect(s) of the most recent anti-cancer treatment to NCI CTCAE Grade 1 or less (except alopecia).
- Patients must have adequate organ and marrow function as defined by initial laboratory tests:
- white blood cell (WBC) ≥ 2000/uL
- absolute neutrophil count (ANC) ≥ 1.5/uL
- Platelets ≥ 100 x 103/uL
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
- Bilirubin ≤ 1.5 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin ≤ 3.0 mg/dL;
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky > 70%;
- Men and women, ages > 18 years of age;
- Life expectancy > 3 months;
- Patients may have brain metastases if these are stable for at least 4 weeks and patients are not steroid dependent;
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study.
- WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL ]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (hCG)) within 72 hours prior to the start of study medication.Men should use avoid impregnating women during study and for 7 mos after the study.
Who cannot join
- Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
- Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic auto immune disease (e.g., rheumatoid arthritis, progressive systemic sclerosis [scleroderma]), systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis];
- Patients with a history of symptomatic interstitial lung disease OR a history of (non-infectious) pneumonitis that required oral or IV steroids or current pneumonitis.
- Patients with active HIV infection Patients with Hepatitis B and Hepatitis C infection.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea;
- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; Tyrosine Kinase inhibitors such as erlotinib;
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- Prior therapy with ipilimumab or another anti-CTLA-4 antagonist;
- Women and men who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 5mos (women) or 7mos(men) weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
Trial locations and contacts
1 site in 1 country.
About this study
NSCLC patients with metastatic disease who have failed at least one prior treatment and have a minimum of two metastatic lesions (at least one measurable), are eligible if they have an ECOG Performance Status of 0-1. Patients will receive on Day 1, ipilimumab (every 6 weeks) concurrently with radiation (6Gy x 5 fractions). Nivolumab (every 2 weeks) will be given in addition to ipilimumab on day 22.
Read the detailed description
NSCLC patients with metastatic disease who have failed at least one prior treatment and have a minimum of two metastatic lesions (at least one measurable), are eligible if they have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Non-ablative radiotherapy (6GyX5) is directed to one lesion during a first immunotherapy treatment with Ipilimumab 3 mg/kg (± 24hrs from first RT dose). On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.
Patients are re-imaged at Week 9 (day 70 ± 7) to evaluate for response (defined as an objective response by RECIST of the measurable metastatic sites outside the radiation field). This response will be evaluated assessing clinical and positron emission computed tomography (PET/CT) responses in the non-irradiated measurable metastatic sites using RECIST 1.1.
- Conditions
- Non Small Cell Lung Cancer Metastatic
- Being tested
- Ipilimumab, Nivolumab, Radiation therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
Ipilimumab (3mg/kg) is given concurrently (+/- 24hrs from first RT dose) with radiation therapy on Day 1 of the study. On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.
NivolumabDrug
Also called OPDIVO
On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.
Radiation therapyRadiation
Ipilimumab (3mg/kg) is given concurrently (+/- 24hrs from first RT dose) with radiation therapy on Day 1 of the study.
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy + Radiation | Experimental | Non-ablative radiotherapy (6GyX5) is directed to one lesion during a first immunotherapy treatment with Ipilimumab 3 mg/kg (± 24hrs from first RT dose). On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression. Receives: Drug: Ipilimumab; Drug: Nivolumab; Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Enhance Overall Response Rate (ORR) to the Combination of Ipi/Nivo in Chemo-refractory NSCLC and Double the ORR of Ipi/RT, From 18% Based on Intent to Treat to 36%.
To enhance the ORR to the combination of Ipi/Nivo in chemo-refractory NSCLC by preceding it with a combination of Ipi/RT to convert the irradiated tumor into an in situ vaccine and to double the ORR of Ipi/RT, from 18% based on intent to treat to 36%.
Measured: 2.5 Months, 6 Months, 3 years
Secondary outcomes (7)
Changes in T-cell Receptor (TCR) Repertoire in Peripheral Blood Are Associated With Response to Treatment
changes in T-cell receptor (TCR) repertoire in peripheral blood are associated with response to treatment
Measured: 4 years
Serum Markers IFN-b, CXCL11, sMICA, sMICB Levels/Changes Associated With Patients' Response to the Treatment.
serum markers interferon-beta(IFN-B), C-X-C motif chemokine 11(CXCL11), soluble major histocompatibility complex class I-related chain A(sMICA), soluble major histocompatibility complex class I-related chain B (sMICB) levels/changes associated with patients' response to the treatment
Measured: 4 years
Associations of Overall Response Rate (ORR) With Changes in the Microbiome
associations of ORR with changes in the microbiome
Measured: 4 years
Progression Free Survival
Patients will be followed for progression free survival.
Measured: 4 years
Patients' Time to Progression Will be Assessed in This Study.
Patients' time to progression will be assessed in this study.
Measured: 3 years
Patients' Duration of Response (DOR) Will be Assessed in This Study.
Patients' duration of response (DOR) will be assessed in this study.
Measured: 3 years
Overall Survival (OS)
Patients will be followed for overall survival.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start9 Oct 2017
- Primary completion11 Mar 2022
- Study completion11 Mar 2022
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- Eligible patients will receive on Day 1 ipilimumab 3mg/kg concurrently with Radiation therapy (6GY x 5 fractions). On Day 22, patients will receive nivolumab 240mg (every 2 weeks) in addition to ipilimumab (1mg/kg). Patients will be evaluated for response at Day 70 (+/- 7 days) for progression.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Silvia Formenti, M.D., Principal investigator, Weill Cornell Medicine New York Prebyterian hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03168464
- Sponsor's protocol ID
- 1607017434
- Status last verified
- Mar 2023
- First submitted
- 19 May 2017
- Last updated
- 24 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiation and Immune Checkpoints Blockade in Metastatic NSCLC (BMS # CA209-632)
- ClinicalTrials.gov ID
- NCT03168464
- Acronym / sponsor ID
- 1607017434
- Conditions
- Non Small Cell Lung Cancer Metastatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 9 Oct 2017 (actual)
- Primary completion
- 11 Mar 2022 (actual)
- Study completion
- 11 Mar 2022 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Posted 24 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
NSCLC patients with metastatic disease who have failed at least one prior treatment and have a minimum of two metastatic lesions (at least one measurable), are eligible if they have an ECOG Performance Status of 0-1. Patients will receive on Day 1, ipilimumab (every 6 weeks) concurrently with radiation (6Gy x 5 fractions). Nivolumab (every 2 weeks) will be given in addition to ipilimumab on day 22.
Detailed description
NSCLC patients with metastatic disease who have failed at least one prior treatment and have a minimum of two metastatic lesions (at least one measurable), are eligible if they have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Non-ablative radiotherapy (6GyX5) is directed to one lesion during a first immunotherapy treatment with Ipilimumab 3 mg/kg (± 24hrs from first RT dose). On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression.
Patients are re-imaged at Week 9 (day 70 ± 7) to evaluate for response (defined as an objective response by RECIST of the measurable metastatic sites outside the radiation field). This response will be evaluated assessing clinical and positron emission computed tomography (PET/CT) responses in the non-irradiated measurable metastatic sites using RECIST 1.1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Eligible patients will receive on Day 1 ipilimumab 3mg/kg concurrently with Radiation therapy (6GY x 5 fractions). On Day 22, patients will receive nivolumab 240mg (every 2 weeks) in addition to ipilimumab (1mg/kg). Patients will be evaluated for response at Day 70 (+/- 7 days) for progression.
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy + Radiation | Experimental | Drug: Ipilimumab, Drug: Nivolumab, Radiation: Radiation therapyNon-ablative radiotherapy (6GyX5) is directed to one lesion during a first immunotherapy treatment with Ipilimumab 3 mg/kg (± 24hrs from first RT dose). On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression. |
Who may qualify
- Ages
- 19 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Ability to understand and the willingness to sign a written informed consent document;
- Histologic diagnosis of NSCLC;
- Any Kras or epidermal growth factor receptor (EGFR) status is permitted; Patients with an EGFR sensitizing mutation must have received an EGFR tyrosine kinase inhibitor (either erlotinib, gefitinib or afatinib) and patients with anaplastic lymphoma kinase (ALK) translocation must have received anti-ALK therapy.
- Patients must have at least two distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter. Patients may have additional non-measurable metastatic lesions (e.g., bone metastases);
- Patients must have prior treatment with at least one line of therapy for metastatic NSCLC. Any prior therapy is permitted except prior therapy with ipilimumab, other anti cytotoxic T-lymphocyte-associated protein (CTLA) agents or Checkpoint inhibitors;
Key exclusion criteria (9 listed)
- Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
- Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic auto immune disease (e.g., rheumatoid arthritis, progressive systemic sclerosis [scleroderma]), systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis];
- Patients with a history of symptomatic interstitial lung disease OR a history of (non-infectious) pneumonitis that required oral or IV steroids or current pneumonitis.
- Patients with active HIV infection Patients with Hepatitis B and Hepatitis C infection.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea;
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 |
|---|---|---|
| IpilimumabAlso: YervoyIpilimumab (3mg/kg) is given concurrently (+/- 24hrs from first RT dose) with radiation therapy on Day 1 of the study. On day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression. | Drug | Immunotherapy + Radiation |
| NivolumabAlso: OPDIVOOn day 22 the combined treatment of ipilimumab plus nivolumab will start (nivolumab 240mg q 2 weeks, ipilimumab 1mg/kg q 6 weeks), and administered until evidence of progression. | Drug | Immunotherapy + Radiation |
| Radiation therapyIpilimumab (3mg/kg) is given concurrently (+/- 24hrs from first RT dose) with radiation therapy on Day 1 of the study. | Radiation | Immunotherapy + Radiation |
Primary outcome
Enhance Overall Response Rate (ORR) to the Combination of Ipi/Nivo in Chemo-refractory NSCLC and Double the ORR of Ipi/RT, From 18% Based on Intent to Treat to 36%.
Time frame: 2.5 Months, 6 Months, 3 years
To enhance the ORR to the combination of Ipi/Nivo in chemo-refractory NSCLC by preceding it with a combination of Ipi/RT to convert the irradiated tumor into an in situ vaccine and to double the ORR of Ipi/RT, from 18% based on intent to treat to 36%.
7 secondary outcomes
Changes in T-cell Receptor (TCR) Repertoire in Peripheral Blood Are Associated With Response to Treatment
Time frame: 4 years
Serum Markers IFN-b, CXCL11, sMICA, sMICB Levels/Changes Associated With Patients' Response to the Treatment.
Time frame: 4 years
Associations of Overall Response Rate (ORR) With Changes in the Microbiome
Time frame: 4 years
Progression Free Survival
Time frame: 4 years
Patients' Time to Progression Will be Assessed in This Study.
Time frame: 3 years
Patients' Duration of Response (DOR) Will be Assessed in This Study.
Time frame: 3 years
Overall Survival (OS)
Time frame: 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Silvia Formenti, M.D. principal investigator
Weill Cornell Medicine New York Prebyterian hospital
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 Ipilimumab, Nivolumab and Radiation therapy in people with Non Small Cell Lung Cancer Metastatic, run by Weill Medical College of Cornell University 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 21 inclusion and 9 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: stopped early, as of the sponsor's last update on 24 Apr 2023. 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?
Yes. Results are posted in the registry (first posted 24 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Enhance Overall Response Rate (ORR) to the Combination of Ipi/Nivo in Chemo-refractory NSCLC and Double the ORR of Ipi/RT, From 18% Based on Intent to Treat to 36%. (time frame: 2.5 Months, 6 Months, 3 years). 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 24 Apr 2023.