A Randomized Phase II Trial of Carboplatin, Paclitaxel, Bevacizumab, With or Without Everolimus for Therapy of Metastatic Malignant Melanoma
Overview
- Phase
- Phase 2
- Intervention
- bevacizumab
- Conditions
- Melanoma (Skin)
- Sponsor
- Alliance for Clinical Trials in Oncology
- Enrollment
- 149
- Locations
- 307
- Primary Endpoint
- Progression-free Survival
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This randomized phase II trial is studying how well carboplatin, paclitaxel, and bevacizumab work when given with or without everolimus in treating patients with malignant melanoma that has spread from where it started to other places in the body. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may block the ability of tumor cells to grow and spread. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy given together with bevacizumab is more effective with or without everolimus in treating patients with metastatic melanoma.
Detailed Description
OBJECTIVES: Primary * To assess whether there is sufficient promise of an impact of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab on progression-free survival that it would be recommended for further testing in patients with metastatic malignant melanoma. Secondary * To estimate the confirmed tumor response rate of each of the treatment regimens. * To estimate the distribution of overall survival (OS) time for each of the treatment regimens. * To assess the impact on the safety profile of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab. OUTLINE: This is a multicenter study. Patients are stratified according to elevated LDH (above upper limit of normal) at baseline (yes vs no), location of metastatic disease (M1a \[skin, subcutaneous tissue, or lymph node only\] vs M1b \[lung\] vs M1c \[other visceral sites\]) and prior chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus orally (PO) once daily (QD) 3 times weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic proof of stage IV malignant melanoma not amenable to surgery; (biopsy can be of locoregional disease in setting of clinically evident stage IV disease, but primary tumor alone will not qualify)
- •At most one prior chemotherapy based regimen for metastatic melanoma (no prior taxane-based regimens allowed); note: prior adjuvant non-taxane based chemotherapy and/or adjuvant immunotherapy are allowed; no limit on the number of prior biologic, immunologic or targeted therapies
- •Measurable disease defined as at least one lesion whose longest diameter can be accurately measured as \>= 2.0 cm with chest x-ray, or as \>= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) scan; note: disease that is measurable by physical examination only is not eligible
- •Life expectancy \>= 4 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Absolute neutrophil count (ANC) \>= 1500/mL
- •Platelets (PLT) \>= 100,000 x 10\^9/L
- •Hemoglobin (Hgb) \>= 9 g/dL (patients may be transfused to meet this requirement)
- •Total cholesterol =\< 300 mg/dL and; (note: serum levels of cholesterol or triglycerides found to be elevated may be lowered with anti-lipid therapy, but must be documented to be below these levels prior to enrollment)
- •Triglycerides =\< 2.5 X upper limit of normal (ULN); (note: serum levels of cholesterol or triglycerides found to be elevated may be lowered with anti-lipid therapy, but must be documented to be below these levels prior to enrollment)
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (bevacizumab, paclitaxel, and carboplatin)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: bevacizumab
Arm I (bevacizumab, paclitaxel, and carboplatin)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: carboplatin
Arm I (bevacizumab, paclitaxel, and carboplatin)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: paclitaxel
Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus)
Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus PO QD on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: bevacizumab
Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus)
Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus PO QD on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: carboplatin
Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus)
Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus PO QD on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: everolimus
Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus)
Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus PO QD on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: paclitaxel
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: Time from randomization to documentation of disease progression or death without documentation of progression;Up to 5 years
The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of disease progression or death without documentation of progression. The distribution of PFS times will be estimated using the Kaplan-Meier method. Progression is defined using the RECIST Criteria as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum of diameters recorded on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm of target lesions, or the appearance of one or more new lesions, unequivocal progression of existing non-target lesions, although unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Secondary Outcomes
- Confirmed Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria(Up to 5 years)
- Overall Survival Time(up to 5 years)
- Toxicity(Up to 5 years)