Sorafenib in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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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. This phase II trial is studying how well sorafenib works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the efficacy of sorafenib, in terms of anti-tumor effects and proportion of clinical responses, in patients with previously untreated unresectable stage III or stage IV melanoma. SECONDARY OBJECTIVES: I. Correlate the efficacy of this drug with the presence of mutant or wild-type BRAF gene in tumors of these patients. II. Determine the toxicity profile of this drug in these patients. III. Correlate serum cryptic collagen epitopes with the extent of tumor burden, invasion, and metastasis in patients treated with this drug. IV. Determine the potential of serum cryptic collagen epitopes to serve as a surrogate marker for monitoring the course of disease in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to presence of BRAF gene mutation in tumor sample (yes vs no). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed annually. PROJECTED ACCRUAL: A total of 26-74 patients (13-37 per stratum) will be accrued for this study within 5.2-18.5 months.

Official Title
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A Phase II Study of BAY 43-9006 (NSC 724772) in Unresectable Stage III and IV Melanoma (IND 69,869)

Conditions
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Stage III Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Drug: sorafenib tosylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed unresectable melanoma Stage III or IV disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan Disease amenable to biopsy (first 13 patients in each stratum only) Brain metastases allowed provided the following criteria are met: Disease has remained radiologically stable for ≥ 6 weeks after completion of whole-brain radiotherapy and remains stable at the time of study entry No mass effect present by radiology No requirement for steroid therapy to control symptoms of brain metastases Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% At least 3 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No evidence of bleeding diathesis AST and ALT ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 2 times ULN Creatinine ≤ 1.5 times ULN No uncontrolled hypertension No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychiatric illness that would preclude study compliance No pre-existing non-hematological dysfunction ≥ grade 2 No ongoing or active infection No history of serious allergic reaction to eggs Able to swallow pills No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or other non-invasive carcinoma No other uncontrolled illness Not specified No prior systemic chemotherapy for metastatic disease See Disease Characteristics See Disease Characteristics No other concurrent investigational agents No concurrent therapeutic anticoagulation No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (sorafenib tosylate)<br>Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (RR) defined as is either a complete or a partial response using RECIST criteria | The overall response rate along with subgroup-specific response rates will be estimated at the end of the trial along with 95% confidence interval. | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Kaplan-Meier estimates will be calculated for time to progression and overall survival, and medians, along with two-sided 95% confidence intervals, will be reported. | From the first day of treatment until the first documentation of disease progression, assessed up to 3.5 years | 
| Toxicity assessed using NCI CTCAE version 3.0 | All adverse events without regard to causal relationship and by causal relationship to study drugs will be summarized. | Up to 3.5 years | 
| Changes in BRAF, P-MAPK, CDK4, and cyclin D1 levels | The proportion of patients with decreases in levels of BRAF, CDK4, or phospho-MAPK will be estimated along with 95% confidence intervals. | Baseline and up to 3.5 years | 
| Overall survival | Kaplan-Meier estimates will be calculated for time to progression and overall survival, and medians, along with two-sided 95% confidence intervals, will be reported. | Up to 3.5 years |