A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma
A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma
RATIONALE: Drugs used in chemotherapy, such as temozolomide, paclitaxel albumin-stabilized nanoparticle formulation, and carboplatin, 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, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether bevacizumab is more effective when given together with temozolomide or paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in killing malignant melanoma cells.
PURPOSE: This randomized phase II trial is studying the side effects of giving temozolomide together with bevacizumab and to see how well it works compared with giving bevacizumab together with paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in treating patients with stage IV malignant melanoma that cannot be removed by surgery.
OBJECTIVES:
Primary
Secondary
Tertiary
OUTLINE: Patients are stratified according to ECOG performance status (0 vs 1) and location of metastatic disease (M1a [skin or subcutaneous tissue or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and randomized to 1 of 2 treatment arms.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for VEGF plasma levels and analysis of changes in immune homeostasis.
Beginning at study entry, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.
Histologic confirmed diagnosis of malignant melanoma
Measurable disease with at least one lesion whose longest diameter canbe measured as ≥ 20 mm by CT or MRI scans OR ≥ 10 mm by spiral CT
No brain metastases per MRI or CT
No radiographically documented invasion of adjacent organs(duodenum, stomach, etc.) or tumor invading major blood vessels
ECOG performance status 0-1
Life expectancy ≥ 4 months
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL (transfusion allowed)
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Total bilirubin ≤ 1.5 mg/dL (unless Gilbert syndrome)
AST ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Urine protein:creatinine ratio < 1.0 at screening ORproteinuria < 2+ by urine dipstick or protein ≤ 1 g by 24-hour urine collection
Negative serum pregnancy test
Not pregnant or nursing
Fertile patients must use effective contraception
Active infection requiring parenteral antibiotics
Poorly controlled high blood pressure (≥ 150 mm Hg systolic and/or100 mm Hg diastolic) despite treatment
NYHA class II-IV congestive heart failure
Serious cardiac arrhythmia requiring medication
Myocardial infarction or unstable angina within the past 6 months
Clinically significant peripheral vascular disease
Deep venous thrombosis or pulmonary embolus within the past year
Active bleeding or pathological conditions that carry high risk of bleeding (e.g., known esophageal varices)
Serious, non-healing wound (including wounds healing by secondary intention), ulcer or bone fracture
Abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within the past 6 months
History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.)
Clinically significant stroke or TIA within the past 6 months
Seizures not controlled with standardmedical therapy
Peripheral neuropathy ≥ grade 2
History of other malignancy within the past 5 years except basal cell or squamous cell carcinoma of the skin treatable with local resection only or carcinoma in situ of the cervix
Significant traumatic injury within the past 4 weeks
History of hypertensive crisis or hypertensive encephalopathy
Active or recent (≤ 30 days) history of hemoptysis (≥ ½ teaspoon of bright red blood per episode)
Known hypersensitivity to any of the components of bevacizumab
Known to be HIV positive
Current or known history of hepatitis
Prior adjuvant chemotherapy and/or immunotherapy for this cancer allowed
No prior treatment with agents disrupting VEGF activity (i.e., bevacizumab,VEGF-trap, anti-VEGFR Mab)
No ongoing need for full-dose oral or parenteral anticoagulation
No ongoing anti-platelet treatment other than low-dose aspirin(i.e., aspirin 81 mg daily)
No other investigational agents within the past 4 weeks
No major surgical procedure or open biopsy within the past 4 weeks
No fine needle aspirations or core biopsies within the past 7 days
No prior chemotherapy in the metastatic setting
No prior treatment with sunitinib malate or sorafenib
No prior treatment with any taxane-based chemotherapy
Patients who have had > 25% of their functional bone marrow irradiated are not eligible for this trial
No adjuvant radiation therapy within the past 4 weeks
More than 2 weeks since prior and no concurrent palliative radiation therapy
No concurrent major surgical procedure
No concurrent participation in another clinical study for procedures or agents that treat the same primary study malignancy
Grand Junction, Colorado 81502, United States
Moline, Illinois 61265, United States
Ottawa, Illinois 61350, United States
Peoria, Illinois 61615, United States
Beech Grove, Indiana 46107, United States
La Porte, Indiana 46350, United States
Des Moines, Iowa 50309, United States
Des Moines, Iowa 50314, United States
Wichita, Kansas 67214, United States
Dearborn, Michigan 48123-2500, United States
Grosse Pointe Woods, Michigan 48236, United States
Minneapolis, Minnesota 55407, United States
Robbinsdale, Minnesota 55422-2900, United States
St Louis, Missouri 63141, United States
Billings, Montana 59101, United States
Missoula, Montana 59807, United States
Allentown, Pennsylvania 18105, United States
Wilkes-Barre, Pennsylvania 18711, United States
Spartanburg, South Carolina 29303, United States
Sioux Falls, South Dakota 57117-5039, United States
Green Bay, Wisconsin 54301-3526, United States