Nab-Paclitaxel and Bevacizumab or Ipilimumab as First-Line Therapy in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT02158520|
Recruitment Status : Completed
First Posted : June 9, 2014
Results First Posted : January 2, 2020
Last Update Posted : January 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Melanoma Mucosal Melanoma Stage IV Cutaneous Melanoma AJCC v6 and v7 Stage IV Uveal Melanoma AJCC v7 Unresectable Melanoma||Biological: Bevacizumab Biological: Ipilimumab Other: Laboratory Biomarker Analysis Drug: Nab-paclitaxel Other: Pharmacological Study||Phase 2|
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.
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.
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 (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase II Study of AB (Nab-Paclitaxel [Abraxane?], Bevacizumab) Versus Ipilimumab for Therapy of Unresectable Stage IV Metastatic Malignant Melanoma|
|Actual Study Start Date :||October 18, 2013|
|Actual Primary Completion Date :||May 24, 2017|
|Actual Study Completion Date :||October 30, 2019|
Experimental: Arm A (bevacizumab and nab-paclitaxel)
Patients receive bevacizumab 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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Experimental: Arm B (ipilimumab)
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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Progression-free Survival (PFS) [ 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 ]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.
- Overall Survival (OS) [ Time Frame: From registration to death due to any cause, assessed up to 4 years ]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.
- Number of Patients With Tumor Response [ Time Frame: Up to 4 years ]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.
- The Number of Patients Who Experienced Toxicity [ Time Frame: Up to 4 years ]The number of patients who experienced toxicity (grade 3 or higher adverse events considered at least possibly related to treatment) are reported below.
- Changes in Biomarkers of Angiogenesis (Arm A) [ Time Frame: Baseline to up to 5 years ]
- Changes in Biomarkers of Immunity [ Time Frame: Baseline to up to 5 years ]
- Pharmacokinetic Changes in Paclitaxel Albumin-stabilized Nanoparticle Formulation Plasma Concentrations [ Time Frame: Baseline, prior to the end of paclitaxel albumin-stabilized nanoparticle formulation infusion, and the morning after nab-paclitaxel infusion on days 1 and 8 of course 1 ]
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): NCT02158520
|United States, California|
|Saint Mary's Medical Center|
|San Francisco, California, United States, 94117|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Illinois|
|University of Illinois|
|Chicago, Illinois, United States, 60612|
|United States, Iowa|
|University of Iowa/Holden Comprehensive Cancer Center|
|Iowa City, Iowa, United States, 52242|
|Siouxland Regional Cancer Center|
|Sioux City, Iowa, United States, 51101|
|United States, Michigan|
|Cancer Research Consortium of West Michigan NCORP|
|Grand Rapids, Michigan, United States, 49503|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Metro Minnesota Community Oncology Research Consortium|
|Saint Louis Park, Minnesota, United States, 55416|
|United States, Nebraska|
|Missouri Valley Cancer Consortium|
|Omaha, Nebraska, United States, 68106|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Wisconsin|
|Saint Vincent Hospital Cancer Center Green Bay|
|Green Bay, Wisconsin, United States, 54301|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Svetomir N Markovic||Academic and Community Cancer Research United|