AVASTM

1
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
• Written informed consent
• Age 18 years
• Able to comply with the protocol
• Patients with histological confirmation of
  completely resected AJCC stage IIB (T3bN0M0
  T4aN0M0), IIC (T4bN0M0) and III (TxN1-3M0)
  cutaneous melanoma
• Patients may or may not have undergone sentinel
  lymph node dissection and/or elective lymph node
  dissection
• Patients must be randomised within 12 weeks of
  completing latest surgery for melanoma
• 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
• Eastern Cooperative Oncology Group (ECOG)
  performance status 0-1
• Life expectancy 6 months
• Adequate haematological function
• Absolute neutrophil count (ANC) 1.5 x 109/L AND
• Platelet count 100 x 109/L AND
• Haemoglobin 9 g/dL (may be transfused to
  maintain or exceed this level)
• Adequate liver function
• Total bilirubin lt1.5 x upper limit of normal
  (ULN) AND Asparagine aminotransferase (AST),
  and/or alanine aminotransferase (ALT) lt2 x ULN
• Adequate renal function
• Serum creatinine 1.25 x ULN or calculated
  creatinine clearance 50 mL/min AND
• Urine dipstick for proteinuria lt2. 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

2
AVAST-M

• Exclusion Criteria
• Non-cutaneous melanoma as the primary disease
  site.
• Any evidence of distant or non-regional lymph
  node metastases.
• Evidence of CNS metastases, even if previously
  treated.
• Incomplete surgical resection of the disease.
• Adjuvant radiotherapy ongoing at randomisation.
• Prior chemotherapy, immunotherapy, or hormonal
  therapy within 12 weeks of randomisation
• Any surgery (including open biopsy, but excluding
  insertion of an indwelling catheter), or
  significant traumatic injury within 28 days prior
  to randomisation, or
• anticipation of the need for surgery during study
  treatment.
• Current or recent (within 7 days of
  randomisation) use of aspirin (gt 300 mg/day).
• Current or recent (within 7 days of
  randomisation) use of full-dose oral or
  parenteral anticoagulants or thrombolytic agent
  for therapeutic purposes.
• Prophylactic use of anticoagulants is allowed.
• History or evidence of inherited bleeding
  diathesis or coagulopathy with the risk of
  bleeding.
• Uncontrolled hypertension (blood pressures
  systolic gt150mmHg and/or diastolic gt100mmHg).
• 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.
• Non-healing wound, active peptic ulcer or bone
  fracture.
• History of abdominal fistula, gastrointestinal
  perforation or intra-abdominal abscess within 6
  months of randomisation.
• Pregnant or breast-feeding females.
• Treatment with any other investigational agent,
  or participation in another clinical trial within
  28 days prior to randomisation.