metastatic melanoma
Conditions
Interventions
Trade Name: Nexavar 200 mg, comprimés pelliculés
Product Name: sorafenib
Pharmaceutical Form: Coated tablet
Trade Name: Temodal 5 mg gélule
Product Name: Temozolomide
Pharmaceutical Form: Capsule, ha
Sponsors
Institut Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Unresectable metastatic stage III or IV melanoma 2) Previously or non-previously treated for metastatic disease 3) Men and women =18 years, WHO performance status of 0 or 1 and life expectancy > 3 months 4) Patients who have at least one uni-dimensional measurable lesion by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST), evaluated within 28 days prior to inclusion. 5) Adequate bone marrow function as assessed by the following laboratory requirements to be conducted within 7 days prior to inclusion: hemoglobin >9.0 g/dl, absolute neutrophil count (ANC)>1,500/mm3, platelets> or = 100,000/mm3. 6) Adequate liver function as assessed by the following laboratory requirements to be conducted within 7 days prior to inclusion: ALT and AST =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Known evolutive CNS tumors including metastatic brain disease. 2) Known or suspected allergy to the investigational agent or dacarbazine or any agent to be administered in the trial. 3) Anti-cancer chemotherapy, immunotherapy (including monoclonal antibodies), hormonal therapy, or investigational drug within 30 days prior to start of study drug. 4) Prior use of temozolomide or sorafenib. 5) Radiotherapy within 3 weeks of start of study drug. 6) Use of biologic response modifiers, such as G-CSF, within 3 weeks of study entry. 7) History of cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); active coronary artery disease (CAD), history of myocardial infarction less than 6 months prior to study entry; cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, uncontrolled hypertension. 8) Active clinically serious infection (> grade 2 NCI-CTCAE version 3.0). 9) Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. 10) Patients with seizure disorder requiring medication (such as anti-epileptics). 11) History of organ allograft. 12) History of lactase deficiency, galactokinase-deficiency galactosemia, glucose or galactose malabsorption syndrome. 13) Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) and any cancer curatively treated > 3 years prior to study entry. 14) Participation in another clinical trial and administration of any investigational drug within 30 days prior to study screening. 15) Pregnant women or breast feeding, women of child-bearing potential. 16) People deprived of freedom or under supervision (including trusteeship). 17) Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study; substance abuse, medical, psychological, social or geographic conditions that may interfere with the patient’s participation in the study or evaluation of the study results. 18) Patients unable to swallow oral medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Definition of the safety profile and maximum tolerated dose (MTD) of sorafenib administered in combination with temozolomide;Secondary Objective: 1.Evaluation of the tumor response rate in patients treated with this combination using the RECIST criteria. 2. Evaluation of the overall survival in patients treated with this combination. 3. Evaluation of the progression-free survival in patients treated with this combination. 4. Evaluation of the effect of this combination on tumor vascularization by DCE-US (Dynamic contrast enhanced ultrasonography). 5. Evaluation of the PK profile of temozolomide in the presence of sorafenib and comparison with the known PK profile of temozolomide. 6. Evaluation of the number and functions of lymphocytes with this combination. 7. Evaluation of the correlation between the tumor response rate and the BRAF mutations in the tumor. 8. Evaluation of the correlation between the response rate and the activity of the 06-methylguanine-DNA-methyltransferase (MGMT) in the tumor. ;Primary end point(s): Safety profile of the association: temozolomide + sorafenib at escalating dose levels. Definition of DLT:The DLT will be defined of appearance of at least one of the following study drugs combination-related event:- Grade 4 neutropenia (absolute neutrophil count less than 500/mm3) for 7 days- febrile neutropenia ( 3 days- Platelet count < 25,000/mm3- Grade 3 or 4 non-hematologic toxicity (excluding grade 3 nausea and vomiting and transient fever) as defined by NCI Common Terminology Criteria version 3.0. | — |
Countries
France
Outcome results
None listed