Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer
- Conditions
- Recurrent Lung Non-Squamous Non-Small Cell CarcinomaMetastatic Lung Non-Squamous Non-Small Cell CarcinomaStage IV Lung Non-Small Cell Cancer AJCC v7
- Interventions
- Registration Number
- NCT03468985
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This partially randomized phase II trial studies how well nivolumab, cabozantinib s-malate, and ipilimumab work in treating patients with stage IV non-small cell lung cancer that has come back. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab, cabozantinib s-malate, and ipilimumab may work better than cabozantinib s-malate alone in treating patients with stage IV non-small cell lung cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To demonstrate whether combination therapy of nivolumab and cabozantinib s-malate (cabozantinib), or of nivolumab and cabozantinib, and ipilimumab as compared to nivolumab alone, extends progression-free survival (PFS) for this patient population with non-squamous non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To estimate the overall survival for each arm of the trial. II. To estimate the best overall response rate for each arm of the trial. III. To estimate the progression free survival of the targeted therapy arm of the trial.
IV. To describe the toxicity profile of monotherapy with nivolumab, and the combination of nivolumab and cabozantinib, and the combination of nivolumab and cabozantinib and ipilimumab, in this patient population with non-squamous NSCLC.
CORRELATIVE OBJECTIVES:
I. To adjust progression free survival for each arm based on PD-L1 tumor status.
IMAGING OBJECTIVES:
I. To describe time point tumor response assessment, overall best response and progression-free survival using the conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the exploratory uni-dimensional immune response criteria (iRRC) and the imaging (i)RECIST criteria with all measurements performed by the central review.
II. To compare RECIST 1.1 imaging response assessment measurements (time point response assessment and overall best response) assess by site study personnel to those performed by central review.
EXPLORATORY TOBACCO USE OBJECTIVES:
I. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported cancer-treatment toxicity (adverse events (both clinical and hematologic) and dose modifications).
II. To determine the effects of tobacco on patient-reported physical symptoms and psychological symptoms.
III. To examine quitting behaviors and behavioral counseling/support and cessation medication utilization.
IV. To explore the effect of tobacco use and exposure on treatment duration, relative dose intensity, and therapeutic benefit.
OUTLINE: Patients are randomized to 1 of 3 arms. Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement are assigned to Arm T.
ARM A: Patients receive nivolumab at 480 mg intravenously (IV) over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive nivolumab at 480 mg IV over 60 minutes on day 1 and cabozantinib s-malate at 40 mg orally (PO) daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive nivolumab at 480 mg IV over 60 minutes on day 1, cabozantinib s-malate at 40 mg PO daily on days 1-28, and ipilimumab at 1 mg/kg IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM T: Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab at 480 mg IV over 60 minutes on day 1 and cabozantinib s-malate at 40 mg PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (nivolumab) Nivolumab Patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm B (nivolumab, cabozantinib) Nivolumab Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm C (nivolumab, cabozantinib, ipilimumab) Ipilimumab Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm C (nivolumab, cabozantinib, ipilimumab) Nivolumab Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm T (Targeted cohort; nivolumab, cabozantinib) Nivolumab Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm B (nivolumab, cabozantinib) Cabozantinib Patients receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm C (nivolumab, cabozantinib, ipilimumab) Cabozantinib Patients receive nivolumab IV over 60 minutes on day 1, cabozantinib s-malate PO daily on days 1-28, and ipilimumab IV over 90 minutes every 8 weeks. Cycles for nivolumab and cabozantinib s-malate repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm T (Targeted cohort; nivolumab, cabozantinib) Cabozantinib Patients with ROS1 gene rearrangement, MET exon 14 splice mutations, MET high amplification, or RET gene rearrangement receive nivolumab IV over 60 minutes on day 1 and cabozantinib s-malate PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Every 3 months up to 4 years and 2 months Progression-free survival is defined as time from randomization to documented disease progression or death from any cause, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions and/or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS will be estimated using the Kaplan-Meier method.
- Secondary Outcome Measures
Name Time Method Overall Survival Every 3 months up to 4 years and 2 months Overall survival is defined as time from randomization to death or date last known alive.
Best Overall Response Every 3 months up to 4 years and 2 months Best overall response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Response is defined as either complete response (CR) or partial response (PR).
Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
For Arm T patients, to be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met. Arm A, B, and C patients do not require confirmation scans for CR or PR.
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Trial Locations
- Locations (468)
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
CHI Saint Vincent Cancer Center Hot Springs
🇺🇸Hot Springs, Arkansas, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
🇺🇸Jonesboro, Arkansas, United States
PCR Oncology
🇺🇸Arroyo Grande, California, United States
Scroll for more (458 remaining)Anchorage Associates in Radiation Medicine🇺🇸Anchorage, Alaska, United States