O6-alkylguanine-DNA-alkyltransferase modulation study Fotemustine plus Temozolomide phase I/II . - ND

• Conditions: metastatic stage III, IV not operable melanoma; MedDRA version: 8.1Level: PTClassification code 10027480Term: Metastatic malignant melanoma

• Registration Number: EUCTR2006-002168-24-IT
• Lead Sponsor: ISTITUTO EUROPEO DI ONCOLOGIA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-11-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Cutaneous mucosal and ocular metastatic melanoma stage III, IV not eligible to surgical treatment; 2. accessible metastases; 3. measurable disease, confirmed by X-Ray, ultrasonography, CT or MRI scans or by clinical measurement in case of superficial lesions; 4. age 18 and 80; 5. ECOG performance status 2; 6. no previous chemotherapy for stage III and IV; 7. at least 4 weeks following previous anticancer medical therapy; 8. no prior radiotherapy within the last 4 weeks before enrollment on the target lesions; 9. if female, not pregnant or lactating. Documentation of a negative serum HCG pregnancy test for women is required prior to enrolment. Women of childbearing potential must use a contraceptive method; 10. adeguate bone marrow function neutrophils 1500/ 956;L; platelets 100,000/ 956;L; haemoglobin 10 g/dL; 11. normal renal and liver function serum creatinine 1.25 X the institution s upper limit of normal ULN ; BUN 25 mg/dL; serum bilirubin 1.25 X ULN; SGOT/AST and SGPT/ALT 1.5 X ULN; alkaline phosphatase 2 X ULN; 12. life expectancy 6 months; 13. signed written informed consent approved by the local Ethics Committee obtained enter in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. No complete recovery from any toxicity due to previous treatments; 2. any other previous in the last 5 years or concurrent cancer, other than resected not melanoma skin cancer or carcinoma in situ of the uterine cervix; 3. patients with symptomatic cerebral or leptomeningeal involvement; 4. any chronic debilitant disease that could interfere with the study treatment and the follow-up; 5. any concomitant treatment with other investigational agents; 6. any uncontrolled intercurrent serious acute or chronic illness ies , bleeding disorders, clinically significant heart disease CTC grade III IV ; 7. any psychological, familiar, sociological or geographical state that could potentially interfere with the study protocol compliance.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: step 1 definition of the maximum tolerated dose of Temozolamide, administered with Fotemustine step 2 verify efficacy and safety of the combination TMZ FTMS TMS will be administered at the dosage defined through step 1 .;Secondary Objective: evaluate AT depletion following TMZ administration in tumor biopsies and in Lymphocites as well as the corelation with TMZ dosage; quantify the number of DNA cross-links induced by FTMS administration and study any corelation with AT levels;Primary end point(s): STEP 1 to define the MTD of the combination of the temozolomide with fotemustine the first drug will be administered two times in the first day of each cycle, that will be repeated every 21 days ; - STEP 2 to assess the rate of objective clinical responses CR or PR .