A Randomized Phase II Trial Comparing Bevacizumab Monotherapy With Dacarbazine (DTIC) in Treatment of Malignant Melanoma, Focusing on Angiogenic Markers and Prevention of Hypertension.

Fecha de inicio: 1 de enero de 2013

Inclusion Criteria: Previously treated or untreated, histologically confirmed, metastatic and unresectable melanoma with progressive disease Both BRAF wild type patients as well as BRAF mutated patients are allowed. For BRAF mutated patients, BRAF targeting agents should be considered in first line if otherwise indicated and no contraindications exist. WHO performance status 0-1 Age >18 years, Known BRAF mutation Able to undergo outpatient treatment Patients must have clinically and/or radiographically documented measurable disease according to RECIST. All radiology studies must be performed within 28 days prior to registration (35 days if negative). At least 4 weeks since adjuvant interferon alpha At least 4 weeks since 1st line treatment in case of metastasis Major surgical procedure or significant traumatic injury > 28 days prior to study treatment start. Biopsy or fine needle aspiration > 2 days prior to study treatment start. Central venous line placement must be inserted at least 2 days prior to treatment start. Only patients with irradiated and asymptomatic brain metastases and off dexamethasone are allowed. Hematology: absolute granulocytes > 1.0 x 109/L Platelets > 100 x 109/L Bilirubin < 1.5 x upper normal limit Serum creatinine < 1.5 x upper normal limits LDH < 1.5 x upper normal limit INR < 1.5 Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial Before patient registration/randomization, written informed consent must be given according to national and local regulations. Exclusion Criteria: No previous DTIC No previous anti-VEGF targeted therapies No pregnant or lactating patients can be included No clinical evidence of coagulopathy No unstable angina pectoris No AV-block II or III without pacemaker No severe congestive heart failure No untreated phaeochromocytoma No severe bradycardia No severe hypotension No severe impairment of peripheral arterial circulation No uncontrolled cardiac arrhythmia No severe asthma or COPD No uncontrolled diabetes mellitus No Angioneurotic edema No severe Aortic valve stenosis No severe hypertrophic cardiomyopathy No severe renal dysfunction No patients on beta blockers/ ACE inhibitors by inclusion unable/unwilling to discontinue beta blockers/ ACE inhibitors and convert to other classes of antihypertensive drugs No full-dose oral coumarin-derived anticoagulants (INR>1.5) or heparin, thrombolytic agents, or chronic, daily treatment with aspirin (>325 mg/day). No uncontrolled hypertension