Patients with stage IV melanoma, previously untreated with chemo- or immuno-therapy for metastatic disease, will be eligible for the study. MedDRA version: 6.1 Level: PT Classification code 10025671
Conditions
Sponsors
ROCHE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed cutaneous malignant melanoma 2. Advanced, inoperable nonchoroidal stage IV melanoma, including unresectable regional lymphatic disease and/or extensive in transit recurrent disease 3. Age 18 4. Performance status 0-1 ECOG 5. Life-expectancy 3 months 6. Measurable and/or evaluable sites of metastases, confirmed by X-Ray, ultrasound, CT scan and NMR at least 1 mm 7. A previous IFN-based immunotherapy in adjuvant setting and/or a vaccination in metastatic setting are allowed however, a wash-out period of at least 4 weeks is requested 8. Normal blood counts ANC 1500/microL and platelet count 150,000/microL , liver function ALT, AST and alkaline phosphatase levels up to 2.5 x upper limit of the normal ranges UNL ; 8804;5 x UNL in case of liver metastases and total bilirubin 3.0 mg/ml; then, alkaline phosphatase 8804;10 x UNL in case of bone metastases and renal function BUN and creatinine levels within the normal ranges, and, in particular, creatinine clearance 50 mL/min or serum creatinine 8804;1.5 x UNL 9. INR 1.5 and APTT 1.5 x UNL 10. Urine dipstick of proteinuria 2 . Patients discovered to have 2 proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate 8804;1 g of protein/24 hrs 11. Written informed consent according to the local Ethics Committee requirements 12. Patients accessibility for treatment and follow-up 13. Complete initial work-up within 4 weeks prior to the beginning of treatment. 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
Exclusion criteria: 1. Prior chemotherapy and/or IFN/IL-2 based immunotherapy for metastatic disease 2. Prior investigational antiangiogenic agents 3. Prior malignancies diagnosed within the last 5 years, with the exception of cured non melanoma skin cancer or adequately treated in situ carcinoma of the cervix. 4. Pregnancy and breast-feeding. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females of childbearing potential unwilling to practice contraception during the study 5. Recent major surgery within 28 days prior to study treatment start 6. Planned radiotherapy for underlying disease 7. Clinical or radiological evidence of CNS metastases 8. Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications 9. Other serious illness or medical condition - Serious non-healing wound or ulcer - Evidence of bleeding diathesis or coagulopathy - Uncontrolled hypertension - Congestive heart failure NYHA grade 2 , prior myocardial infarction or cerebrovascular accidents within 6 months, unstable angina, serious cardiac arrhythmia requiring medication - History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent - Infections requiring i.v. antibiotics and tuberculosis under treatment for entering the trial - Active or latent autoimmune diseases a determination of anti-thyreoglobulin and antinuclear antibodies is requested for entering the trial - Ongoing treatment with aspirin 325 mg/day or other medications known to predispose to gastrointestinal ulceration - Current or recent within 10 days prior to study treatment start ongoing treatment with full-dose anticoagulants for therapeutic purpose - Active peptic ulcer, unstable diabetes mellitus, cirrhosis and other significant uncontrolled illness, which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the preliminary antitumor activity in terms of overall response rate complete and partial responses of bevacizumab in combination with fotemustine.;Secondary Objective: To evaluate toxicity and the safety profile of the combination To evaluate duration of response DR , time to progression TTP , time to treatment failure TTF , and overall survival OS .;Primary end point(s): - Complete remission CR complete disappearance of all previously detectable disease for a period of at least 28 days, and no new lesions. - Partial remission PR more than 30 decrease in the sum of the longest diameters of all target lesions for a period of at least 28 days, and no new lesions. - Stable Disease SD neither sufficients strinkage to qualify for PR nor sufficient increase to qualify for PD. - Progressive disease PD an increase of more than 20 in the sum of the longest diameter of target lesions, or the appearance of disease at any sites. - Time to progression TTP will be measured from the first day of treatment until to the first observation of disease progression or death due to any cause or the last date the patient was known to be progression free or alive. - Overall survival OS will be computed as the time between the first day of treatment and the date of death or the last date the patient was known to be alive. - Adverse events, laboratory parameters. | — |
Countries
Italy
Outcome results
None listed