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
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
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
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.
Inclusion 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])
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (Phase I)
Safety Issue:
Yes
Principal Investigator
Caroline Robert, MD
Investigator Affiliation:
Gustave Roussy, Cancer Campus, Grand Paris
Authority:
United States: Federal Government
Study ID:
CDR0000626803
NCT ID:
NCT00811759
Start Date:
June 2007
Completion Date:
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- stage III melanoma
- recurrent melanoma
- Melanoma
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