This randomized phase II trial studies how well aldesleukin with or without ziv-aflibercept works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Aldesleukin may stimulate the white blood cells to kill cancer. Ziv-aflibercept may stop the growth of melanoma by blocking blood flow to the tumor. It is not yet known whether aldesleukin is more effective with or without ziv-aflibercept in treating melanoma.
PRIMARY OBJECTIVES: I. Test the hypothesis that combination biotherapy with aflibercept (ziv-aflibercept) and high-dose (HD) interleukin (IL)-2 (aldesleukin) will improve the progression-free survival compared to HD IL-2 alone. SECONDARY OBJECTIVES: I. Evaluate the response rate (complete response \[CR\] + partial response \[PR\]) of aflibercept and HD IL-2 as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 and compare to results of HD IL-2 alone. II. Evaluate the toxicities and tolerance of combination biotherapy with aflibercept and HD IL-2 and maintenance aflibercept alone in this patient population and compare to HD-IL2 alone. III. Test the hypotheses related to the laboratory correlative studies. IV. Evaluate the overall survival of patients treated with aflibercept and HD IL-2 and HD IL-2 alone. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive ziv-aflibercept intravenously (IV) over at least 1 hour on day 1 of weeks 1, 3, 5, and 7 (and in week 9 of course 1 only) and high-dose aldesleukin IV over 15 minutes every 8 hours for 5 days in weeks 1 and 3 (and in weeks 3 and 5 of course 1 only). Treatment repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising ziv-aflibercept IV on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive high-dose aldesleukin IV over 15 minutes every 8 hours for 5 days in weeks 1 and 3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-4 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
City of Hope Comprehensive Cancer Center
Duarte, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
IU Health Methodist Hospital
Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
...and 11 more locations
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: The time from the date of randomization until date of progression, death, or recurrence, assessed up to 5 years
Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
Time frame: Until Death from any cause, up to 5 years
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (RR) = CR + PR.
Time frame: Up to 5 years
Count of Participants With Adverse Events
Count of the number of participants with grade 3 \& 4 adverse events attributed to treatment agents. Events are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Time frame: Up to 5 years
Progression-free Survival for Patients With High Vascular Endothelial Growth Factor (VEGF) Levels
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median baseline measure for VEGF were used as the cut point for "low" vs "high" VEGF groups.
Time frame: Up to 5 years
Progression-free Survival for Patients With Low VEGF Levels
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median baseline measure for VEGF were used as the cut point for "low" vs "high" VEGF groups.
Time frame: Up to 5 years
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