AVAST-M Protocol Title A randomised trial evaluating the VEGF inhibitor, Bevacizumab (Avastin®),as adjuvant therapy following resection of AJCC stage IIB (T3bN0M0 & T4aN0M0), IIC (T4bN0M0) and III (TxN1-3M0) cutaneous melanoma. Inclusion Criteria 1.Written informed consent 2.Age ≥18 years 3.Able to comply with the protocol 4.Patients with histological confirmation of completely resected AJCC stage IIB (T3bN0M0 & T4aN0M0), IIC (T4bN0M0) and III (TxN1-3M0) cutaneous melanoma 5.Patients may or may not have undergone sentinel lymph node dissection and/or elective lymph node dissection 6.Patients must be randomised within 12 weeks of completing latest surgery for melanoma 7.For patients with resected stage IIB or IIC disease, when wide local excision is undertaken after resection of primary melanoma, the interval between the two procedures must not exceed 12 weeks 8.Eastern Cooperative Oncology Group (ECOG) performance status Life expectancy ≥ 6 months 10.Adequate haematological function: 1.Absolute neutrophil count (ANC) ≥1.5 x 109/L AND 2.Platelet count ≥100 x 109/L AND 3.Haemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level) 11.Adequate liver function: 1.Total bilirubin <1.5 x upper limit of normal (ULN) AND Asparagine aminotransferase (AST), and/or alanine aminotransferase (ALT) <2 x ULN 12.Adequate renal function: 1.Serum creatinine ≤1.25 x ULN or calculated creatinine clearance ≥50 mL/min AND 2.Urine dipstick for proteinuria <2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours AND Prothrombin time (PT) and Partial thromboplastin time (PTT/aPTT) ≤1.5 x ULN 13.Negative pregnancy test (serum or urine dipstick) for women of child bearing potential (WOCBP) 14.Adequate contraception

AVAST-M Exclusion Criteria 1.Non-cutaneous melanoma as the primary disease site. 2.Any evidence of distant or non-regional lymph node metastases. 3.Evidence of CNS metastases, even if previously treated. 4.Incomplete surgical resection of the disease. 5.Adjuvant radiotherapy ongoing at randomisation. 6.Prior chemotherapy, immunotherapy, or hormonal therapy within 12 weeks of randomisation 7.Any surgery (including open biopsy, but excluding insertion of an indwelling catheter), or significant traumatic injury within 28 days prior to randomisation, or 8.anticipation of the need for surgery during study treatment. 9.Current or recent (within 7 days of randomisation) use of aspirin (> 300 mg/day). 10.Current or recent (within 7 days of randomisation) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. 11.Prophylactic use of anticoagulants is allowed. 12.History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. 13.Uncontrolled hypertension (blood pressures: systolic >150mmHg and/or diastolic >100mmHg). 14.Clinically significant (i.e. active) cardiovascular disease for example CVA (≤6 months before randomisation), myocardial infarction (≤6 months before randomisation), unstable angina, congestive heart failure NYHA Class ≥II, serious cardiac arrhythmia requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication. 15.Non-healing wound, active peptic ulcer or bone fracture. 16.History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of randomisation. 17.Pregnant or breast-feeding females. 18.Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to randomisation. 19.Known hypersensitivity to bevacizumab or any of its excipients. 20.Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications. 21. Any condition, which, in the opinion of the investigator, might interfere with the safety of the patient or evaluation of the study objectives. 22.Previous malignancy in the last 5 years except completely excised basal cell cancer of the skin or completely excised squamous cell cancer of the skin (Patients with completely excised in situ malignancies are eligible).