Randomized Phase II Study of AB (Abraxane™, Bevacizumab) Versus Ipilimumab for 1st Line Therapy of Unresectable Stage IV Metastatic Malignant Melanoma (BRAF V600E Negative)
PRIMARY OBJECTIVES:
I. To assess whether the combination nab-paclitaxel (paclitaxel albumin-stabilized
nanoparticle formulation) and bevacizumab (AB) prolongs progression-free status relative to
ipilimumab as a 1st line 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 first line 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 1st treatment course.
III. To estimate whether the tumor response rate differs with respect to 2nd treatment
course for those who progressed during their first treatment course.
IV. To further examine the safety profile of each of these regimens.
TERTIARY 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 paclitaxel albumin-stabilized nanoparticle formulation 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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS)
The distribution of PFS times for each treatment arm will be estimated using the Kaplan-Meier method. A stratified log-rank test and Cox partial likelihood score test will be used to assess whether the distribution of PFS times differ with respect to treatment arm having adjusted for M stage (M1c vs. else) and gender. For PFS, Cox modeling with the partial likelihood score tests will be used to examine the strength of association between these time to event distributions and additional potential prognostic factors.
From randomization to the earliest documentation of progression as defined by the RECIST criteria (version 1.1) or death from any cause without the documentation of progression, assessed up to 5 years
No
Svetomir Markovic, M.D., Ph.D.
Study Chair
Academic and Community Cancer Research United
United States: Food and Drug Administration
RU261206I
NCT01879306
September 2013
Name | Location |
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Mayo Clinic | Rochester, Minnesota 55905 |