Randomized Phase II Study of AB (Nab-Paclitaxel [Abraxane?], Bevacizumab) Versus Ipilimumab for Therapy of Unresectable Stage IV Metastatic Malignant Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Metastatic Melanoma
- Sponsor
- Academic and Community Cancer Research United
- Enrollment
- 24
- Locations
- 13
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic or cytologic proof of surgically unresectable stage IV malignant melanoma - including that of uveal and mucosal origin
- •Note: biopsy can be of locoregional disease in setting of clinically evident stage IV disease; a biopsy of the primary tumor alone does not fulfill this requirement
- •No more than 2 prior courses of systemic therapy for metastatic melanoma
- •For patients with metastatic melanoma not of uveal origin, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation determination using a Clinical Laboratory Improvement Amendments (CLIA)-approved testing method on metastatic tumor tissue
- •NOTE: patients with metastatic melanoma of uveal origin do not need to have formal BRAF testing due to low probability of a BRAF V600 mutation in their metastatic tumor
- •Measurable disease; note: disease that is measurable by physical examination only is not eligible
- •Life expectancy of \>= 4 months
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •Absolute neutrophil count \>=1500/mL (obtained =\< 14 days prior to registration/randomization)
- •Platelet count \>= 100,000 x 10\^9/L (obtained =\< 14 days prior to registration/randomization)
Exclusion Criteria
- •Brain metastases per magnetic resonance imaging (MRI) or computed tomography (CT)
- •Note: patients who have had therapy for brain metastasis (i.e., surgical resection, whole brain radiation, or stereotactic radiosurgery \[SRS\] even if stable) are not eligible
- •Other investigational agents =\< 4 weeks prior to registration/ randomization
- •Anti-cancer therapy (including immunotherapy) =\< 4 weeks prior to registration/randomization; exception: adjuvant Leukine =\< 14 days prior to registration/randomization
- •Prior treatment in the adjuvant or metastatic setting with any of the following:
- •Agents disrupting VEGF activity or targeting vascular endothelial growth factor receptor (VEGFR);
- •Ipilimumab;
- •Or taxane based chemotherapy regimens (including paclitaxel, docetaxel, cabazitaxel or nab-paclitaxel)
- •Major surgical procedure, open biopsy, or significant traumatic injury =\< 4 weeks prior to registration/randomization; (port-a-cath placement does not count as a major surgical procedure and patients can be enrolled at any time after placement)
- •Fine needle aspirations or core biopsies =\< 7 days prior to registration/ randomization
Arms & Interventions
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.
Intervention: Bevacizumab
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Nab-paclitaxel
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.
Intervention: Pharmacological Study
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.
Intervention: Ipilimumab
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall Survival (OS)(From registration to death due to any cause, assessed up to 4 years)
- Number of Patients With Tumor Response(Up to 4 years)
- The Number of Patients Who Experienced Toxicity(Up to 4 years)