Aldesleukin With or Without Ziv-Aflibercept in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery
Stage IIIA Skin Melanoma
Stage IIIB Skin Melanoma
Stage IIIC Skin Melanoma
Stage IV Skin Melanoma
Other: Laboratory Biomarker Analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Study of Sequential Biotherapy With Aflibercept and High Dose IL-2 Versus High Dose IL-2 Alone in Patients With Inoperable Stage III or Stage IV Melanoma: Efficacy and Biomarker Study|
- Progression-free survival [ Time Frame: The time from the date of randomization until date of progression, death, or recurrence, assessed up to 5 years ] [ Designated as safety issue: No ]The primary comparison will be based on the log-rank test for comparison of progression-free survival, which will be estimated by the Kaplan-Meier method. Cox regression will also be conducted for progression-free survival.
- 1-year survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]Cox regression will be conducted for survival.
- Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Toxicity will be primarily be evaluated by examining the number of doses of aldesleukin administered during the first course of combination therapy; the percentage of patients who receive all 56 doses will also be summarized. The toxicity after the scheduled 10th dose of aldesleukin, the frequency of grade III and IV toxicities, and unusual toxicities will also be summarized.
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Cox regression will be conducted for survival. Survival endpoints will be evaluated from data of randomization and will be also reported on the as-treated populations for comparison.
- Response rate, evaluated using the RECIST v1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Response rate will be estimated and a 95% confidence interval (CI) provided for each arm.
- Changes in VEGF levels [ Time Frame: Baseline up to 5 years ] [ Designated as safety issue: No ]Explored using multivariate Cox regression.
|Study Start Date:||January 2011|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm I (ziv-aflibercept and aldesleukin)
Patients receive ziv-aflibercept IV over at least 1 hour in 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.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Ziv-Aflibercept
Experimental: Arm II (aldesleukin)
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.
Other Names:Other: Laboratory Biomarker Analysis
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01258855
|United States, California|
|City of Hope Comprehensive Cancer Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Sanjay Awasthi 626-359-8111 ext 69200 firstname.lastname@example.org|
|Principal Investigator: Sanjay Awasthi|
|USC / Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Heinz-Josef Lenz 323-865-3955 email@example.com|
|Principal Investigator: Heinz-Josef Lenz|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Scott D. Christensen 916-734-3772 firstname.lastname@example.org|
|Principal Investigator: Scott D. Christensen|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900 Skhehler@cohmg.com|
|Principal Investigator: Stephen C. Koehler|
|United States, Colorado|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Karl D. Lewis 720-848-0584 email@example.com|
|Principal Investigator: Karl D. Lewis|
|United States, Georgia|
|Emory University/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: David H. Lawson 404-778-1900 firstname.lastname@example.org|
|Principal Investigator: David H. Lawson|
|United States, Illinois|
|Lurie Children's Hospital-Chicago||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Timothy M. Kuzel 312-695-4518 email@example.com|
|Principal Investigator: Timothy M. Kuzel|
|United States, Indiana|
|IU Health Methodist Hospital||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Theodore F. Logan 317-948-7576 firstname.lastname@example.org|
|Principal Investigator: Theodore F. Logan|
|United States, Iowa|
|University of Iowa/Holden Comprehensive Cancer Center||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Mohammed M. Milhem 319-356-2324 email@example.com|
|Principal Investigator: Mohammed M. Milhem|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Lawrence E. Flaherty 313-576-8725 firstname.lastname@example.org|
|Principal Investigator: Lawrence E. Flaherty|
|United States, Minnesota|
|Metro Minnesota Community Oncology Research Consortium||Recruiting|
|Saint Louis Park, Minnesota, United States, 55416|
|Contact: Patrick J. Flynn 612-863-8585 email@example.com|
|Principal Investigator: Patrick J. Flynn|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Lionel D. Lewis 603-650-8685 firstname.lastname@example.org|
|Principal Investigator: Lionel D. Lewis|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Saby George 716-845-8387 Saby.George@RoswellPark.org|
|Sub-Investigator: Saby George|
|United States, Ohio|
|Cleveland Clinic Foundation||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Marc S. Ernstoff 216-444-0888 email@example.com|
|Principal Investigator: Marc S. Ernstoff|
|Case Western Reserve University||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Henry B. Koon 216-368-1175 Henry.Koon@UHhospitals.org|
|Principal Investigator: Henry B. Koon|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Thomas E. Olencki 614-293-4680 Thomas.Olencki@osumc.edu|
|Principal Investigator: Thomas E. Olencki|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033-0850|
|Contact: Chandra P. Belani 717-531-1078 firstname.lastname@example.org|
|Principal Investigator: Chandra P. Belani|
|University of Pittsburgh Cancer Institute (UPCI)||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Ahmad A. Tarhini 412-648-6507 email@example.com|
|Principal Investigator: Ahmad A. Tarhini|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Igor Puzanov 615-936-6938 firstname.lastname@example.org|
|Principal Investigator: Igor Puzanov|
|United States, Virginia|
|University of Virginia Cancer Center||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Geoffrey R. Weiss 434-243-0066 email@example.com|
|Principal Investigator: Geoffrey R. Weiss|
|Principal Investigator:||Ahmad Tarhini||Beckman Research Institute|