This randomized phase II trial studies how well nab-paclitaxel and bevacizumab or ipilimumab works as first-line therapy in treating patients with stage IV melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may stop the growth of tumor cells by binding to a protein called vascular endothelial growth factor (VEGF) and by preventing the growth of new blood vessels that tumors need to grow. Ipilimumab blocks a substance called cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) on the surface of T cells and may help the immune system kill cancer cells. It is not yet known whether nab-paclitaxel and bevacizumab is more effective than ipilimumab in treating melanoma.
PRIMARY OBJECTIVES: I. To assess whether the combination nab-paclitaxel and bevacizumab (AB) prolongs progression-free status relative to ipilimumab as a treatment in patients with unresectable stage IV melanoma. SECONDARY OBJECTIVES: I. To estimate the hazard of death among those randomized to AB then ipilimumab relative to those randomized to ipilimumab then AB as treatment in patients with unresectable stage IV melanoma. II. To assess whether tumor response rate (as determined by Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria 1.1) differs with respect to first (1st) treatment course. III. To estimate whether the tumor response rate differs with respect to second (2nd) treatment course for those who progressed during their first treatment course. IV. To further examine the safety profile of each of these regimens. CORRELATIVE OBJECTIVES: I. To examine the pharmacokinetics of nab-paclitaxel when combined with bevacizumab therapy. II. To examine pharmacodynamic changes of blood-derived parameters (biomarkers) of angiogenesis and immunity as a function of therapy. III. To examine whether changes in serum biomarkers are also seen in the tumor. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks. ARM B: Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks. After completion of study treatment, patients are followed up for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Given IV
Given IV
Correlative studies
Given IV
Correlative studies
Saint Mary's Medical Center
San Francisco, California, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Illinois
Chicago, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Siouxland Regional Cancer Center
Sioux City, Iowa, United States
Cancer Research Consortium of West Michigan NCORP
Grand Rapids, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Missouri Valley Cancer Consortium
Omaha, Nebraska, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
...and 3 more locations
Progression-free Survival (PFS)
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From randomization to the earliest documentation of progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) or death from any cause without the documentation of progression, assessed up to 4 years
Overall Survival (OS)
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time frame: From registration to death due to any cause, assessed up to 4 years
Number of Patients With Tumor Response
Tumor response defined as complete or partial response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR): Disappearance of all evidence of disease, Partial response (PR): Regression of measurable disease and no new sites.
Time frame: Up to 4 years
The Number of Patients Who Experienced Toxicity
The number of patients who experienced toxicity (grade 3 or higher adverse events considered at least possibly related to treatment) are reported below.
Time frame: Up to 4 years
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