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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: July 12, 2005
Last updated: January 14, 2013
Last verified: January 2013
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

Condition Intervention Phase
Stage III Melanoma
Stage IV Melanoma
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of BAY 43-9006 (NSC 724772) in Unresectable Stage III and IV Melanoma (IND 69,869)

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Response rate (RR) defined as is either a complete or a partial response using RECIST criteria [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    The overall response rate along with subgroup-specific response rates will be estimated at the end of the trial along with 95% confidence interval.

Secondary Outcome Measures:
  • Time to progression [ Time Frame: From the first day of treatment until the first documentation of disease progression, assessed up to 3.5 years ] [ Designated as safety issue: No ]
    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.

  • Toxicity assessed using NCI CTCAE version 3.0 [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: Yes ]
    All adverse events without regard to causal relationship and by causal relationship to study drugs will be summarized.

  • Changes in BRAF, P-MAPK, CDK4, and cyclin D1 levels [ Time Frame: Baseline and up to 3.5 years ] [ Designated as safety issue: No ]
    The proportion of patients with decreases in levels of BRAF, CDK4, or phospho-MAPK will be estimated along with 95% confidence intervals.

  • Overall survival [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
    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.

Estimated Enrollment: 74
Study Start Date: June 2005
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


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.


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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00119249

United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Anna Pavlick Montefiore Medical Center
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00119249     History of Changes
Other Study ID Numbers: NCI-2012-02659  NYWCCC-NYU-0438  N01CM62204  CDR0000434613 
Study First Received: July 12, 2005
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Antineoplastic Agents
Enzyme Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protein Kinase Inhibitors
Vitamin B Complex
Vitamins processed this record on May 24, 2016