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

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00811759
• Other study ID #: CDR0000626803
• Secondary ID: IGR-CSET-2006/12
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: December 18, 2008
• Last updated: October 6, 2010
• Start date: June 2007

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Drug:
• sorafenib tosylate

• temozolomide

Genetic:
• gene expression analysis

• mutation analysis

Other:
• laboratory biomarker analysis

• pharmacological study

Procedure:
• biopsy

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (Phase I)			Yes
Primary	Progression-free survival at 12 weeks (Phase II)			No