RATIONALE: 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, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving carboplatin and paclitaxel together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin and paclitaxel together with bevacizumab works in treating patients with stage IV melanoma that cannot be removed by surgery.

Condition	Intervention	Phase
Recurrent Melanoma Stage IV Melanoma	Drug: bevacizumab  Drug: carboplatin  Drug: paclitaxel  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy	Phase II

Further study details as provided by National Cancer Institute (NCI):

OBJECTIVES:

Primary

• Determine the anti-tumor activity of carboplatin, paclitaxel, and bevacizumab, in terms of progression-free survival, in patients with unresectable stage IV melanoma.
• Determine the toxicity profile of this regimen in these patients.

Secondary

• Determine the distribution of overall survival times in patients treated with this regimen.
• Determine the response rate in patients treated with this regimen.
• Determine the changes in blood levels of vascular endothelial growth factor in patients treated with this regimen.
• Determine the changes in immune homeostasis in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV over 30 minutes on day 1, paclitaxel IV over 1 hour on days 1, 8, and 15, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed melanoma
• Unresectable stage IV disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No radiologically confirmed invasion of adjacent organs (e.g., duodenum or stomach)
• No tumor invasion of major blood vessels
• No history of primary brain tumor or other CNS disease
• No brain metastases by MRI or CT scan

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• More than 4 months

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed)
• No active bleeding

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• INR ≤ 1.5 times ULN
• PTT normal
• No known esophageal varices

Renal

• Creatinine ≤ 1.5 times ULN
• Urine protein creatinine ratio ≤ 0.5 OR
• Urine protein < 1 g/24-hr urine collection

Cardiovascular

• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No myocardial infarction within the past 6 months
• No unstable angina within the past 6 months
• No clinically significant peripheral vascular disease
• No uncontrolled hypertension (i.e., blood pressure ≥ 150/90 mm Hg despite antihypertensive therapy)
• No clinically significant stroke within the past 6 months
• No deep vein thrombosis within the past year
• No other vascular abnormality

Pulmonary

• No pulmonary embolus within the past year

Gastrointestinal

• No history of abdominal fistula
• No gastrointestinal perforation
• No intra-abdominal abscess within the past 4 weeks

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy
• No other pathological condition that would confer a high risk of bleeding
• No active infection requiring parenteral antibiotics
• No serious nonhealing wound (including wounds healing by secondary intention), ulcer, or bone fracture
• No peripheral neuropathy ≥ grade 2
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to the study drugs
• No uncontrolled seizures
• No other uncontrolled illness
• No significant traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior antivascular endothelial growth factors (VEGF), including any of the following:
• Bevacizumab
• VEGF Trap
• Anti-VEGF receptor monoclonal antibody
• Small molecular tyrosine kinase inhibitors of VEGF receptors

Chemotherapy

• No more than 1 prior chemotherapy regimen
• No prior carboplatin or paclitaxel
• No other concurrent chemotherapy

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to > 25% of bone marrow
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgical procedure or open biopsy
• At least 1 week since prior fine-needle aspiration or core biopsy
• No concurrent major surgery

Other

• More than 4 weeks since prior systemic therapy
• No concurrent full-dose oral or parenteral anticoagulation
• No concurrent antiplatelet therapy except low-dose aspirin (i.e., 81 mg of oral aspirin daily) allowed
• No other concurrent experimental drugs

Please refer to this study by ClinicalTrials.gov identifier  NCT00255762

Study chairs or principal investigators

Svetomir Markovic, MD, PhD,  Study Chair,  Mayo Clinic   
Daniel Nikcevich, MD, PhD,  St. Mary''''s - Duluth Clinic Cancer Center   
Mark R. Pittelkow, MD,  Mayo Clinic   
Daniel Nikcevich, MD, PhD,  St. Mary''''s - Duluth Clinic Cancer Center   
Barbara A. Pockaj, MD,  Mayo Clinic Scottsdale   
Henry C. Pitot, MD,  Mayo Clinic   
Edward T. Creagan, MD,  Mayo Clinic   
Michael K. Gornet, MD,  Mayo Clinic Scottsdale   
Lori A. Erickson, MD,  Mayo Clinic   
Judith S. Kaur, MD,  Mayo Clinic   
James N. Ingle, MD,  Mayo Clinic   

Study ID Numbers:  CDR0000449967; NCCTG-N047A
Last Updated:  December 8, 2005
Record first received:  November 18, 2005
ClinicalTrials.gov Identifier:  NCT00255762
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-01-10