Description:
This randomized phase III trial compares nivolumab with ipilimumab and nivolumab alone in
treating patients with stage IV squamous cell lung cancer that has come back after previous
treatment. This is a "non-match" sub-study that includes all screened patients not eligible
for a biomarker-driven sub-study. Monoclonal antibodies, such as nivolumab and ipilimumab,
may be able to shrink tumors. It is not yet known whether nivolumab works better with or
without ipilimumab in treating patients with squamous cell lung cancer.
Title
- Brief Title: Lung-MAP: Nivolumab With or Without Ipilimumab as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers
- Official Title: A Phase III Randomized Study of Nivolumab Plus Ipilimumab Versus Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer and No Matching Biomarker (Lung-Map Sub-Study)
Clinical Trial IDs
- ORG STUDY ID:
S1400I
- SECONDARY ID:
NCI-2016-00050
- SECONDARY ID:
S1400I
- SECONDARY ID:
S1400I
- SECONDARY ID:
S1400I
- SECONDARY ID:
U10CA180888
- NCT ID:
NCT02785952
Conditions
- Recurrent Squamous Cell Lung Carcinoma
- Stage IV Squamous Cell Lung Carcinoma AJCC v7
Interventions
| Drug | Synonyms | Arms |
|---|
| Ipilimumab | Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy | Arm I (nivolumab, ipilimumab) |
| Nivolumab | BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo | Arm I (nivolumab, ipilimumab) |
Purpose
This randomized phase III trial compares nivolumab with ipilimumab and nivolumab alone in
treating patients with stage IV squamous cell lung cancer that has come back after previous
treatment. This is a "non-match" sub-study that includes all screened patients not eligible
for a biomarker-driven sub-study. Monoclonal antibodies, such as nivolumab and ipilimumab,
may be able to shrink tumors. It is not yet known whether nivolumab works better with or
without ipilimumab in treating patients with squamous cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To compare overall survival (OS) in patients with advanced stage refractory squamous cell
carcinoma (SCCA) of the lung randomized to nivolumab plus ipilimumab versus nivolumab.
SECONDARY OBJECTIVES:
I. To compare investigator-assessed progression-free survival (IA-PFS) in patients with
advanced stage refractory SCCA of the lung randomized to nivolumab plus ipilimumab versus
nivolumab.
II. To compare the response rates (confirmed and unconfirmed, complete and partial) per
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among patients randomized to
receive nivolumab plus ipilimumab versus nivolumab.
III. To compare the response rates (confirmed only, complete and partial) per RECIST 1.1
among patients randomized to receive nivolumab plus ipilimumab versus nivolumab.
IV. To evaluate the frequency and severity of toxicities associated with nivolumab plus
ipilimumab versus nivolumab.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To evaluate if there is a differential treatment effect on OS, IA-PFS, and response by
tumor programmed death-ligand 1 (PD-L1) expression status.
II. To examine patient reported outcomes by treatment arm.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab
IV over 60 minutes on day 1 of every third course (every 42 days). Courses repeat every 14
days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days
in the absence of disease progression or unacceptable toxicity.
After completion of study treatment but prior to disease progression, patients are followed
up every 3 months for 1 year and then every 6 months for up to 3 years. After disease
progression, patients are followed up every 6 months for 2 years and at end of year 3 after
sub-study registration.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm I (nivolumab, ipilimumab) | Experimental | Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course (every 42 days). Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | |
| Arm II (nivolumab) | Active Comparator | Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | |
Eligibility Criteria
Inclusion Criteria:
- Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON
ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master
Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
- Patients must have been assigned to S1400I
- Patients must not have had prior treatment with an anti-programmed cell death (PD)-1,
anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4
antibody, or any other antibody or drug specifically targeting T-cell costimulation or
immune checkpoint pathways
- Patients must not have an active, known, or suspected autoimmune disease; patients are
permitted to enroll if they have vitiligo, type I diabetes mellitus, hypothyroidism
only requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger
- Patients must not have any known allergy or reaction to any component of the nivolumab
and ipilimumab formulations
- Patients must not have received systemic treatment with corticosteroids (> 10 mg daily
prednisone or equivalent) or other immunosuppressive medications within 14 days prior
to sub-study registration; inhaled or topical steroids, and adrenal replacement doses
=< 10 mg daily prednisone or equivalent are permitted in the absence of active
autoimmune disease
- Patients must not have a known positive test for hepatitis B virus surface antigen
(HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or
chronic infection; patients with a positive hepatitis C antibody with a negative viral
load are allowed
- Patients must not have known history of testing positive for human immunodeficiency
virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Patients must not have interstitial lung disease that is symptomatic or disease that
may interfere with the detection or management of suspected drug-related pulmonary
toxicity
- Patients must also be offered participation in banking for future use of specimens
- Patients must have a lipase, amylase, TSH with reflex free T3/T4 performed within 7
days prior to sub-study registration
- Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, and myocardial infarction
within 6 months, or serious uncontrolled cardiac arrhythmia
- Patients with a history of congestive heart failure (CHF) or at risk because of
underlying cardiovascular disease or exposure to cardiotoxic drug should have an
electrocardiogram (EKG) and echocardiogram performed to evaluate cardiac function
as clinically indicated
- Patients with evidence of congestive heart failure (CHF), myocardial infarction
(MI), cardiomyopathy, or myositis should have a cardiac evaluation including lab
tests and cardiology consultations as clinically indicated including EKG,
creatine phosphokinase (CPK), troponin, and echocardiogram
- Patients who can complete Patient Reported Outcomes (PRO) forms in English are
required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire
and a pre-study S1400I European Quality of Life Five Dimension (EQ-5D) Questionnaire
within 14 days prior to registration; NOTE: Patients enrolled to S1400I prior to
9/1/2016 are not eligible for the PRO study
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (Design #1, Phase II) |
| Time Frame: | From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual |
| Safety Issue: | |
| Description: | A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. |
Secondary Outcome Measures
| Measure: | Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (Design #1, Phase III) |
| Time Frame: | From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years |
| Safety Issue: | |
| Description: | Will compare between the two arms. |
| Measure: | Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (Design #1, Phase II and III) |
| Time Frame: | Up to 3 years |
| Safety Issue: | |
| Description: | Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level. |
| Measure: | Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III) |
| Time Frame: | Up to 3 years |
| Safety Issue: | |
| Description: | Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Southwest Oncology Group |
Last Updated
September 16, 2020
