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

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

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

Study Overview

• Status: Completed
• Conditions: Stage IV Melanoma; Stage III Melanoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: sorafenib tosylate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (sorafenib tosylate); Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anna Pavlick, Montefiore Medical Center

Publications and helpful links

General Publications

• Ott PA, Hamilton A, Min C, Safarzadeh-Amiri S, Goldberg L, Yoon J, Yee H, Buckley M, Christos PJ, Wright JJ, Polsky D, Osman I, Liebes L, Pavlick AC. A phase II trial of sorafenib in metastatic melanoma with tissue correlates. PLoS One. 2010 Dec 29;5(12):e15588. doi: 10.1371/journal.pone.0015588.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: July 12, 2005
• First Submitted That Met QC Criteria: July 12, 2005
• First Posted (Estimate): July 13, 2005

Study Record Updates

• Last Update Posted (Estimate): January 15, 2013
• Last Update Submitted That Met QC Criteria: January 14, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2012-02659; N01CM62204 (U.S. NIH Grant/Contract); NYWCCC-NYU-0438; CDR0000434613 (Registry Identifier: PDQ (Physician Data Query))