Clinical Drug Experience Knowledgebase

Criteria

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