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

Primary Purpose

Melanoma (Skin)

Status

Unknown status

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

sorafenib tosylate

temozolomide

gene expression analysis

mutation analysis

laboratory biomarker analysis

pharmacological study

biopsy

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage IV melanoma, stage III melanoma, recurrent melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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])

Sites / Locations

Institut Gustave Roussy

Outcomes

Primary Outcome Measures

Maximum tolerated dose (Phase I)

Progression-free survival at 12 weeks (Phase II)

Secondary Outcome Measures

Full Information

NCT ID

NCT00811759

First Posted

December 18, 2008

Last Updated

October 6, 2010

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

1. Study Identification

Unique Protocol Identification Number

NCT00811759

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

July 2009

Overall Recruitment Status

Unknown status

Study Start Date

June 2007 (undefined)

Primary Completion Date

May 2009 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

4. Oversight

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma (Skin)

Keywords

stage IV melanoma, stage III melanoma, recurrent melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Masking

None (Open Label)

Enrollment

58 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

sorafenib tosylate

Intervention Type

Drug

Intervention Name(s)

temozolomide

Intervention Type

Genetic

Intervention Name(s)

gene expression analysis

Intervention Type

Genetic

Intervention Name(s)

mutation analysis

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Type

Other

Intervention Name(s)

pharmacological study

Intervention Type

Procedure

Intervention Name(s)

biopsy

Primary Outcome Measure Information:

Title

Maximum tolerated dose (Phase I)

Title

Progression-free survival at 12 weeks (Phase II)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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])

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Caroline Robert, MD

Organizational Affiliation

Gustave Roussy, Cancer Campus, Grand Paris

Facility Information:

Facility Name

Institut Gustave Roussy

City

Villejuif

ZIP/Postal Code

F-94805

Country

France

12. IPD Sharing Statement

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

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