Carboplatin, Paclitaxel, and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00255762

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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. 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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Melanoma Stage IV Melanoma	Drug: carboplatin Drug: paclitaxel Biological: bevacizumab Other: laboratory biomarker analysis	Phase 2

Detailed Description

OBJECTIVES: Primary I. 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 I. Determine the distribution of overall survival times in patients treated with this regimen.

Determine the response rate in patients treated with this regimen. III. 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Carboplatin, Weekly Paclitaxel and Biweekly Bevacizumab in Patients With Unresectable Stage IV Melanoma

Study Start Date :

Dec 1, 2005

Actual Primary Completion Date :

Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (carboplatin, paclitaxel, bevacizumab) 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.	Drug: carboplatin Given IV Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin Drug: paclitaxel Given IV Other Names: Anzatax Asotax TAX Taxol Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (carboplatin, paclitaxel, bevacizumab)

Drug: carboplatin

Given IV

Other Names:

Carboplat

CBDCA

JM-8

Paraplat

Paraplatin

Drug: paclitaxel

Given IV

Other Names:

Anzatax

Asotax

TAX

Taxol

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Progression free survival [Time from registration to documentation of disease progression, assessed up to 8 weeks]
Constructed using the properties of the binomial distribution. Estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Confirmed tumor response (complete response or partial response) [Up to 5 years]
A ninety percent confidence interval for the true proportion of confirmed tumor responses will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution.
Clinical response rate [Up to 5 years]
A ninety percent confidence interval for the true clinical response rate will be calculated.
Overall survival [Time is defined as the time from registration to death due to any cause, assessed up to 5 years]
The distribution of survival time will be estimated using the method of Kaplan-Meier.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed melanoma
Unresectable stage IV disease
Evidence of metastatic 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
Performance status - ECOG 0-2
More than 4 months
Absolute granulocyte count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL (transfusion allowed)
No active bleeding
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
Creatinine ≤ 1.5 times ULN
Urine protein creatinine ratio ≤ 0.5
Urine protein < 1 g/24-hr urine collection
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 mmHg despite antihypertensive therapy)
No clinically significant stroke within the past 6 months
No deep vein thrombosis within the past year
No other vascular abnormality
No pulmonary embolus within the past year
No history of abdominal fistula
No gastrointestinal perforation
No intra-abdominal abscess within the past 4 weeks
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
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
No more than 1 prior systemic chemotherapy regimen
No prior carboplatin or paclitaxel
No other concurrent chemotherapy
More than 4 weeks since prior radiotherapy
No prior radiotherapy to > 25% of bone marrow
No concurrent radiotherapy
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
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