Nonsmall Cell Lung CancerPhase 2NCT04625699
Study of Durvalumab + Tremelimumab in NSCLC Patients After Adjuvant Treatment
A Phase 2 study testing Durvalumab and Tremelimumab in people with Nonsmall Cell Lung Cancer, run by Catherine Shu.
Trial summary
The purpose of this study is to determine whether it is feasible and safe to give research participants investigational treatment with durvalumab and tremelimumab after they have completed standard treatment for NSCLC and once they have detectable circulating tumor DNA (ctDNA) in the blood before there is evidence of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonsmall Cell Lung Cancer
- What is being tested?
- Durvalumab and Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2022to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 greater than or equal to 18 years
- Patients must have pathologically confirmed NSCLC; no mixed NSCLC/SCLC histology allowed
- Stage II-IIIB (8th edition) disease who have undergone surgical resection, excluding patients with N3 disease
- Must have documentation that the tumor does not harbor an activating EGFR mutation, ALK gene rearrangement, or a ROS1 gene rearragement
- Must have adequately recovered from the toxicity and/or complications of surgery prior to initiation of durvalumab+tremelimumab
- Detectable ctDNA at a mutant allele frequency of >0.1% after surgical resection and completion of adjuvant treatment
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- No evidence of clinical disease on CT chest/abdomen/pelvis at the time of ctDNA detection
- Completed standard of care adjuvant treatment at least two weeks prior to day 1 of durvalumab+tremelimumab
- Archived tumor tissue: formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin block or at least 10 unstained slides, with an associated pathology report.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g. Health Insurance Portability and Accountability Act) must be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following agespecific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and folliclestimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Body weight > 30 kg
- Must have a life expectancy of at least 12 weeks
- Ability to comply with the study protocol, in the investigator's judgment
- Adequate organ and marrow function
Who cannot join
- Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) or herbal therapy is acceptable.
- History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of immune therapy and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease; malignancy undergoing active surveillance per stand of care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score 6, and prostate-specific antigen [PSA] 10 mg/mL, etc.)
- Any unresolved toxicity NCI CTCAE v.5.0 Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with Grade 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
- Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (RECIST)) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF
- History of allergic reactions attributed to compounds of similar chemical or biologic
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- Patients with active hepatitis B or C infections or a history of HIV infection. These participants will be ineligible due to potential for worsening of infection with the use of immunotherapy. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- History of active primary immunodeficiency
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: Patients with vitiligo or alopecia; hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; any chronic skin condition that does not require systemic therapy; patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician; celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, including TB, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure, excluding lung cancer resection, during the course of the study
- Administration of a live, attenuated vaccine within 30 days before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study.
- Patients, if enrolled, should not receive live vaccine whilst receiving treatment and up to 30 days after durvalumab, tremelimumab administration.
- History of interstitial lung disease or pneumonitis of any cause
- Pregnant women are excluded from this study because durvalumab and tremelimumab are investigational agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab and tremelimumab, breastfeeding should be discontinued if the mother is treated with durvalumab and tremelimumab.
About this study
Official title: A Feasibility Study of Durvalumab + Tremelimumab in Resected Non Small Cell Lung Cancer (NSCLC) Patients With Detectable Circulating Tumor DNA After Adjuvant Treatment
The purpose of this study is to determine whether it is feasible and safe to give research participants investigational treatment with durvalumab and tremelimumab after they have completed standard treatment for NSCLC and once they have detectable circulating tumor DNA (ctDNA) in the blood before there is evidence of disease recurrence on imaging studies. These investigational agents are a type of immunotherapy, which is a treatment that activates your own body's immune system to treat cancer.
Read the detailed description
This is an open label, single arm, pilot study of adjuvant durvalumab+ tremelimumab (D+T) for patients with stage II-IIIB (excluding N3) NSCLC.The trial will evaluate the feasibility of adjuvant D+T in patients who have undergone surgical resection and standard of care (SOC) adjuvant treatment and subsequently develop detectable plasma ctDNA. 15 evaluable patients will be enrolled. Patients with resected stage II-IIIB (excluding N3) NSCLC who have completed adjuvant standard of care treatment will be pre-screened and consented for the trial. They will undergo ctDNA testing with the Signatera assay at the completion of adjuvant treatment and every 4 months thereafter with standard CT imaging assessment up to 1 year. Patients with detectable ctDNA at a mutant allele frequency of >0.1% and no evidence of recurrence on CT imaging will be enrolled in the trial. They will receive durvalumab every 4 weeks for 4 cycles and tremelimuamb on cycles 1 and 3 with concomitant plasma ctDNA quantification. Patients will be followed with standard CT imaging of the chest as well as routine and exploratory blood tests every 4 months until 1 year after completion of D+T. They will also be followed for up to 3 years for determination of DFS and OS.
- Conditions
- Nonsmall Cell Lung Cancer
- Being tested
- Durvalumab, Tremelimumab
- Keywords
- II-IIIB
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736, IMFINZI
4 doses of Durvalumab 1500 mg IV Day 1, q28 days (For example, interventions involving drugs may include dosage form, dosage, frequency, and duration.)
TremelimumabDrug
Also called formerly CP-675,206
2 doses of Tremelimumab 300 mg IV Day 1, q56 days
| Study group | Role | What they receive |
|---|---|---|
| durvalumab+ tremelimumab | Experimental | durvalumab will be administered Q4weeks and tremelimumab will be administered Q8 weeks Receives: Drug: Durvalumab; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of evaluable patients enrolled
To assess the feasibility of identifying and recruiting patients for adjuvant treatment with durvalumab+tremelimumab (D+T) in the setting of molecular residual disease based on ctDNA positivity after surgical resection and standard of care treatment for stage II-IIIB NSCLC. The target is a total of 15 with a projected accrual rate of 2-3 patients per month.
Measured: 36 months
Secondary outcomes (4)
ctDNA clearance
To assess the dynamics of ctDNA in response to treatment with adjuvant durvalumab+tremelimumab. This will be reported with 95% confidence intervals based on the exact binomial distribution.
Measured: 36 months
Overall survival
To determine the duration of overall survival with adjuvant durvalumab+tremelimumab
Measured: Up to 36 months
Disease free survival
To determine the duration of disease free survival with adjuvant durvalumab+tremelimumab
Measured: Up to 36 months
Adverse events rate
To evaluate the safety of adjuvant D+T, adverse events will be scored according to NCI CTCAE v5.0 and their frequency and nature will be tabulated by categories. This will be reported with 95% confidence intervals based on the exact binomial distribution.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study startDec 2022 (estimated)
- Primary completionJul 2023 (estimated)
- Study completionDec 2023 (estimated)
Why it stopped: Contract was never finalized.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonsmall Cell Lung CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Shu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Catherine Shu, Columbia University
- Investigators
- Catherine Shu, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04625699
- Sponsor's protocol ID
- AAAT0800
- Status last verified
- Jun 2023
- First submitted
- 6 Nov 2020
- Last updated
- 6 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Study of Durvalumab + Tremelimumab in Resected Non Small Cell Lung Cancer (NSCLC) Patients With Detectable Circulating Tumor DNA After Adjuvant Treatment
- ClinicalTrials.gov ID
- NCT04625699
- Acronym / sponsor ID
- AAAT0800
- Conditions
- Nonsmall Cell Lung Cancer
- Keywords
- II-IIIB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Contract was never finalized.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Catherine ShuUniversity, hospital or other
- Study start
- Dec 2022 (estimated)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 12 Nov 2020 (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.
The purpose of this study is to determine whether it is feasible and safe to give research participants investigational treatment with durvalumab and tremelimumab after they have completed standard treatment for NSCLC and once they have detectable circulating tumor DNA (ctDNA) in the blood before there is evidence of disease recurrence on imaging studies. These investigational agents are a type of immunotherapy, which is a treatment that activates your own body's immune system to treat cancer.
Detailed description
This is an open label, single arm, pilot study of adjuvant durvalumab+ tremelimumab (D+T) for patients with stage II-IIIB (excluding N3) NSCLC.The trial will evaluate the feasibility of adjuvant D+T in patients who have undergone surgical resection and standard of care (SOC) adjuvant treatment and subsequently develop detectable plasma ctDNA. 15 evaluable patients will be enrolled. Patients with resected stage II-IIIB (excluding N3) NSCLC who have completed adjuvant standard of care treatment will be pre-screened and consented for the trial. They will undergo ctDNA testing with the Signatera assay at the completion of adjuvant treatment and every 4 months thereafter with standard CT imaging assessment up to 1 year. Patients with detectable ctDNA at a mutant allele frequency of >0.1% and no evidence of recurrence on CT imaging will be enrolled in the trial. They will receive durvalumab every 4 weeks for 4 cycles and tremelimuamb on cycles 1 and 3 with concomitant plasma ctDNA quantification. Patients will be followed with standard CT imaging of the chest as well as routine and exploratory blood tests every 4 months until 1 year after completion of D+T. They will also be followed for up to 3 years for determination of DFS and OS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| durvalumab+ tremelimumab | Experimental | Drug: Durvalumab, Drug: Tremelimumabdurvalumab will be administered Q4weeks and tremelimumab will be administered Q8 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age greater than or equal to 18 years
- Patients must have pathologically confirmed NSCLC; no mixed NSCLC/SCLC histology allowed
- Stage II-IIIB (8th edition) disease who have undergone surgical resection, excluding patients with N3 disease
- Must have documentation that the tumor does not harbor an activating EGFR mutation, ALK gene rearrangement, or a ROS1 gene rearragement
- Must have adequately recovered from the toxicity and/or complications of surgery prior to initiation of durvalumab+tremelimumab
Key exclusion criteria (16 listed)
- Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) or herbal therapy is acceptable.
- History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of immune therapy and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease; malignancy undergoing active surveillance per stand of care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score 6, and prostate-specific antigen [PSA] 10 mg/mL, etc.)
- Any unresolved toxicity NCI CTCAE v.5.0 Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with Grade 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
- Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (RECIST)) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF
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 |
|---|---|---|
| DurvalumabAlso: MEDI4736, IMFINZI4 doses of Durvalumab 1500 mg IV Day 1, q28 days (For example, interventions involving drugs may include dosage form, dosage, frequency, and duration.) | Drug | durvalumab+ tremelimumab |
| TremelimumabAlso: formerly CP-675,2062 doses of Tremelimumab 300 mg IV Day 1, q56 days | Drug | durvalumab+ tremelimumab |
Primary outcome
Number of evaluable patients enrolled
Time frame: 36 months
To assess the feasibility of identifying and recruiting patients for adjuvant treatment with durvalumab+tremelimumab (D+T) in the setting of molecular residual disease based on ctDNA positivity after surgical resection and standard of care treatment for stage II-IIIB NSCLC. The target is a total of 15 with a projected accrual rate of 2-3 patients per month.
4 secondary outcomes
ctDNA clearance
Time frame: 36 months
Overall survival
Time frame: Up to 36 months
Disease free survival
Time frame: Up to 36 months
Adverse events rate
Time frame: 36 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2023.
- 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.
Catherine Shu, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab and Tremelimumab in people with Nonsmall Cell Lung Cancer, run by Catherine Shu.
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 17 inclusion and 16 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: withdrawn, as of the sponsor's last update on 6 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of evaluable patients enrolled (time frame: 36 months). 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 6 Jun 2023.