Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase III trial is studying carboplatin, paclitaxel, and sorafenib to see how well they work compared to carboplatin and paclitaxel in treating patients with unresectable stage III or stage IV melanoma. 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. Sorafenib 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 giving carboplatin and paclitaxel together with sorafenib is more effective than carboplatin and paclitaxel in treating melanoma

Further Study Information

PRIMARY OBJECTIVES:

I. To compare the overall survival of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib.

II. To compare progression-free survival, response rate, and safety of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib.

III. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib including angiogenesis, monooxygenases polymorphisms and MDR.

IV. To assess the association of expression markers in the patient tumor with clinical outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive oral sorafenib twice daily on days 2-19.

Arm II: Patients receive paclitaxel and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 2-19.

In both arms, treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or who achieve a partial response or complete response may continue to receive sorafenib or placebo alone twice daily on days 1-21. Courses with sorafenib or placebo repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years

Eligibility Criteria

Inclusion Criteria:

• Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have a history of cutaneous, mucosal or unknown primary site

• Patients who have received prior systemic cytotoxic chemotherapy for treatment of melanoma are ineligible; the following groups are eligible with regard to prior systemic therapy either in the adjuvant or metastatic disease setting:

• No prior therapy

• Immunotherapy consisting of Interferon, Interleukin-2, GM-CSF or vaccine

• One prior investigational therapy (cannot be chemotherapy or an inhibitor of Ras, Raf, or MEK) NOTE: Chemotherapy given via isolated limb perfusion is allowed

• Prior radiation therapy is allowed; however, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions

• All sites of disease must be evaluated within 4 weeks of registration; patients must have measurable disease as defined by RECIST

• ECOG performance status of 0 or 1

• White blood count >= 3,000/mm^3

• Absolute granulocyte count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Serum creatinine =< 2.0 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40ml/min (neither drug is cleared by the kidney)

• Total Bilirubin =< 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease)

• INR =< 1.5 and a PTT within normal limits (patients who are on therapeutic anticoagulation with warfarin should have documentation of a normal PT/PTT prior to initiating that therapy)

• Patients must not have ocular melanoma

• Patients must have discontinued immunotherapy or radiation therapy at least 4 weeks prior to initiation of treatment and recovered from adverse events due to those agents

• Patients must not receive any other investigational agents during the period on study or the four weeks prior to initiation of treatment

• Patients must not have a history or clinical evidence of brain metastasis; patients must be evaluated with a head MRI within 4 weeks prior to enrollment

• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease free for >= 5 years prior to the time of randomization

• Patients must not have any evidence of bleeding diathesis

• Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's Wort

• Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk

• All females of childbearing potential must have a blood test or urine study within 4 weeks prior to registration to rule out pregnancy

• The effects of sorafenib, carboplatin and paclitaxel on the developing human fetus are unknown; for this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well

• HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with sorafenib, carboplatin or paclitaxel is unknown; appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Keith Flaherty

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00110019
Information obtained from ClinicalTrials.gov on December 27, 2012

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