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

October 6, 2010 updated by: Gustave Roussy, Cancer Campus, Grand Paris

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • 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)

Secondary

  • 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

Enrollment (Anticipated)

58

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, F-94805
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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])

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose (Phase I)
Progression-free survival at 12 weeks (Phase II)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

Investigators

  • Caroline Robert, MD, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Anticipated)

May 1, 2009

Study Registration Dates

First Submitted

December 18, 2008

First Submitted That Met QC Criteria

December 18, 2008

First Posted (Estimate)

December 19, 2008

Study Record Updates

Last Update Posted (Estimate)

October 7, 2010

Last Update Submitted That Met QC Criteria

October 6, 2010

Last Verified

July 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000626803
  • IGR-CSET-2006/1261
  • IGR-SORAF-TEM ST1
  • INCA-RECF0818
  • EUDRACT-2007-00527-18
  • SCHER-IGR-CSET-2006/1261
  • BAYER-IGR-CSET-2006/1261

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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