Previously treated or untreated histologically confirmed metastatic and unresectable melanoma with radiological (RECIST), clinical or biochemical progressive disease. MedDRA version: 14.1 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Avastin (Bevacizumab)
Product Name: Bevacizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg/k
Sponsors
Helse Bergen HF, Haukeland University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Previously treated or untreated histologically confirmed metastatic and unresectable melanoma with radiological (RECIST), clinical or biochemical progressive disease - No previous DTIC - No previous anti-VEGF targeted therapies - WHO performance status 0-1 - Age >18 years, - No pregnant or lactating patients can be included. - 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 - Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start. Biopsy or fine needle aspiration within 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 dexametasone are allowed. - Hematology: absolute granulocytes > 1.0 x 109/L - Platelets > 100 x 109/L - Bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Propranolol contraindications: 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 - Enalapril contraindications: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to compare efficacy of bevacizumab monotherapy with standard chemotherapy (DTIC) in patients with metastatic or unresectable malignant melanoma. ;Secondary Objective: Secondary objectives: -To prospectively evaluate the predictive value of a set of predefined candidate angiogenic markers associated with vascular endothelial growth factor (VEGF) dependent angiogenesis. -To estimate the time to progression, survival and proportion of patients with stable disease. -To indentify mechanisms causing acquired resistance to treatment with bevacizumab and escape mechanisms caused by other angiogenic growth factors than VEGF. -To analyze safety and influence on outcome variables by primary prevention of bevacizumab induced hypertension, by low dose beta blockers (propranolol 40 mg x 2), in comparison with an ACE inhibitor (enalapril 5 mg x 1). ;Primary end point(s): Primary endpoint: Progression free survival (PFS) at 6 months ;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint: Secondary endpoint are overall response (OR) rates according to RECIST, disease Control (DC: CR+PR+ SD) at 6 months and overall survival (OS). Additional secondary endpoints are safety and tolerability (adverse events) as well as influence (PFS, OR, DC) of primary prevention of bevacizumab induced hypertension by propranolol versus enalapril. ;Timepoint(s) of evaluation of this end point: Median 6 months. Range 1-40 months. | — |
Countries
Norway
Contacts
Public ContactOddbjørn Straume
Haukeland University Hospital, Helse Bergen
Outcome results
None listed