Sorafenib and Temozolomide in Treating Patients With Stage III or Stage IV Melanoma - Full Text View

Sponsored by:	Institut Gustave Roussy
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00811759

Purpose

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	Intervention	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 I Phase II

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Temozolomide Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled
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

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

Primary Outcome Measures:

Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
Progression-free survival at 12 weeks (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment:	58
Study Start Date:	June 2007
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

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

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])

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811759

Locations

France
Institut Gustave Roussy	Recruiting
Villejuif, France, F-94805
Contact: Caroline Robert, MD 33-1-4211-4339

Sponsors and Collaborators

Institut Gustave Roussy

Investigators

Investigator:

Caroline Robert, MD

Institut Gustave Roussy

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

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
Study First Received:	December 18, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00811759 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
stage III melanoma
recurrent melanoma

Study placed in the following topic categories:

Temozolomide
Protein Kinase Inhibitors
Recurrence
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Nevus, Pigmented
Neuroepithelioma
Nevus
Antineoplastic Agents, Alkylating
Sorafenib
Alkylating Agents

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Protein Kinase Inhibitors
Temozolomide
Pharmacologic Actions
Melanoma

Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Sorafenib
Alkylating Agents

ClinicalTrials.gov processed this record on May 07, 2009