Sorafenib and Temozolomide in Treating Patients With Stage III or Stage IV Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00811759
Recruitment Status : Unknown
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : December 19, 2008
Last Update Posted : October 7, 2010
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: 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. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with temozolomide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving sorafenib together with temozolomide in treating patients with stage III or stage IV melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Drug: sorafenib tosylate Drug: temozolomide Genetic: gene expression analysis Genetic: mutation analysis Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy Phase 1 Phase 2

Detailed Description:



  • Determine the safety profile and the maximum tolerated dose of sorafenib tosylate and temozolomide in patients with stage III-IV melanoma. (Phase I)
  • Evaluate progression-free survival at 12 weeks. (Phase II)


  • Evaluate tumor response according to RECIST criteria.
  • Evaluate overall and progression-free survival.
  • Evaluate the effect of treatment on tumor vascularization.
  • Compare the pharmacokinetic profile of temozolomide with and without sorafenib tosylate.
  • Evaluate the number and the role of lymphocytes.
  • Correlate tumor response rate with BRAF mutation status.
  • Correlate response rate with MGMT activity.
  • Compare the efficacy of genomics and proteomics as a means of discovery of serum biomarkers.
  • Study the prognostic and predictive value of circulating endothelial cells and circulating endothelial progenitors.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients receive oral sorafenib tosylate twice daily on days 1-28 (days 8-28 of course 1) and oral temozolomide once daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with accessible tumors (cutaneous or sub-cutaneous) undergo biopsies at baseline and day 28 for analysis of BRAF mutations and MGMT expression.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Single Center, Uncontrolled Phase I/II Study Evaluating the Safety and Maximum Tolerated Dose of Daily Sorafenib Administered in Combination With Prolonged Temozolomide in Patients With Metastatic Melanoma
Study Start Date : June 2007
Estimated Primary Completion Date : May 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Primary Outcome Measures :
  1. Maximum tolerated dose (Phase I)
  2. Progression-free survival at 12 weeks (Phase II)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of unresectable or metastatic melanoma

    • Stage III or IV disease
  • Previously treated or untreated metastatic disease
  • At least one unidimensionally measurable lesion by RECIST criteria by scan or MRI
  • No concurrent brain or CNS metastases


  • WHO performance status 0-1
  • Life expectancy ≥ 3 months
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin > 9 g/dL
  • PT, INR, and PTT < 1.5 times upper limit of normal (ULN)
  • Transaminases < 2.5 times ULN (< 5 in the case of liver metastases)
  • Amylase and lipase < 1.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • Serum creatinine < 1.5 times ULN
  • Normal respiratory, cardiac, and neurological function
  • Not pregnant or nursing
  • No history of any of the following cardiac conditions:

    • NYHA class II-IV heart failure
    • Coronary disease
    • Myocardial infarction within the past 6 months
    • Cardiac arrhythmia requiring treatment with something other than beta-blockers or digoxin
    • Severe uncontrolled hypertension
  • No severe active infection > grade 2
  • No epilepsy requiring medical treatment
  • No other cancer except for carcinoma in situ of the cervix, basal cell carcinoma, superficial bladder tumors, or curatively treated cancer > 3 years ago
  • No HIV or hepatitis B or C positivity
  • No lactase or galactokinase deficiency, galactose intolerance, or disease accompanied by malabsorption of glucose or galactose
  • No allergy to the study drugs or to dacarbazine
  • Able to swallow medications
  • No patients deprived of liberty
  • No psychological, familial, social, or geographic conditions that would preclude clinical follow up


  • See Disease Characteristics
  • No prior organ transplantation
  • No prior temozolomide or sorafenib tosylate
  • More than 30 days since other prior antitumor chemotherapy, immunotherapy, hormonal therapy, or investigational agent
  • More than 30 days since prior study drugs
  • More than 3 weeks since prior radiotherapy
  • More than 3 weeks since prior biological response modifiers (i.e., filgrastim [G-CSF])

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00811759

Institut Gustave Roussy
Villejuif, France, F-94805
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
OverallOfficial: Caroline Robert, MD Gustave Roussy, Cancer Campus, Grand Paris Identifier: NCT00811759     History of Changes
Other Study ID Numbers: CDR0000626803
First Posted: December 19, 2008    Key Record Dates
Last Update Posted: October 7, 2010
Last Verified: July 2009

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
stage III melanoma
recurrent melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents