Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02785952
Recruitment Status : Recruiting
First Posted : May 30, 2016
Last Update Posted : August 31, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma AJCC v7 Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Nivolumab Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 18, 2015
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm I (nivolumab, ipilimumab)
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.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Active Comparator: Arm II (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Less than 33% improvement in median investigator-assessed progression-free survival as defined as Response Evaluation Criteria in Solid Tumors version 1.1 (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 18 months since completion of accrual ]
    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. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.

  3. Overall survival [ Time Frame: Up to 3 years ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.

  4. Overall survival (Design #1, Phase III) [ Time Frame: From date of sub-study registration (or date of screening registration if patient never enrolls in a sub-study) to date of death due to any cause, assessed up to 3 years ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival, comparing the two treatment arms. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.


Secondary Outcome Measures :
  1. 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 ]
    Will compare between the two arms.

  2. 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 ]
    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.

  3. 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 ]
    Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate.


Other Outcome Measures:
  1. Screen success rate [ Time Frame: Up to 3 years ]
    Monitored by the percentage of screened patients that register to a therapeutic sub-study.

  2. Treatment arm randomization acceptance rate [ Time Frame: Up to 3 years ]
    Monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02785952


  Show 1207 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Vassiliki Papadimitrakopoulou Southwest Oncology Group

Layout table for additonal information
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02785952     History of Changes
Other Study ID Numbers: S1400I
NCI-2016-00050 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1400I
S1400I ( Other Identifier: SWOG )
S1400I ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: May 30, 2016    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018

Layout table for additional information
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents