Melanoma Case Control Protocol Summary The study will assemble and follow up a population based cohort of a total of upto 2000 cutaneous melanoma patients aged from 18 to 75 years. They will be newly diagnosed patients with primary tumours in the period 2000 till A subset of patients with rare variants of melanoma of any breslow thickness (such as acral lentiginous, sub-ungual, ENT, oropharyngeal, perineal, vaginal, vulval, rectal and nodal disease with no known primary) will also be recruited. Eligibility Criteria 1.Melanoma cases with breslow thickness ≥ 0.75mm will be ascertained from various centres. The cases will be aged between 18 and 75 years and will have had an invasive melanoma. That is, that patients with in situ lesions/MIN lesions and lesions with breslow thickness <0.75mm will be excluded. Patients with lentigo maligna melanoma will be included. Patients throughout the uk with rare melanomas or undergoing sentinel node biopsy are also eligible subject to local R&D approval. Contact with these patients will only be made via their clinician. Occasionally there may be patients who refer themselves, for example having seen the study on the NCRN website, in which case a reply will be made to them directly. 2.The subset of rare melanomas will be recruited from various regions in the UK in the same manner as 1a, except there will be no upper age limit, or a limit on the date of recruitment post diagnosis, due to the small number of eligible patients. To give significant numbers, the intention will be to recruit these cases nationally and beyond 2008 to 2010, dependent upon funding. For all melanoma trials mentioned, contact details are: Alison Hassall: Ex4939Fran Lawton:

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).