Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Philippa Corrie
ORCID ID
Contact details
Oncology Centre
Box 193
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 216083
pippa.corrie@addenbrookes.nhs.uk
Additional identifiers
EudraCT number
2006-005505-64
ClinicalTrials.gov number
Protocol/serial number
2006-005505-64
Study information
Scientific title
A randomised trial evaluating the vascular endothelial growth factor inhibitor, bevacizumab (AVASTin®), as adjuvant therapy following resection of American Joint Committee on Cancer (AJCC) stage IIB (T4aN0M0), IIC (T4bN0M0) and III (TxN1-2M0) cutaneous Melanoma
Acronym
AVAST-M
Study hypothesis
To determine the overall survival of patients treated with bevacizumab, compared with standard observation after resection of high risk melanoma.
Ethics approval
Oxford C Multi-centre Research Ethics Committee, ref: 07/Q1606/15 - approval pending
Study design
Randomised phase III multi-centre prospective clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Cutaneous melanoma
Intervention
After resection of the high risk melanoma, patients will be given 7.5 mg per Kg bevacizumab by Intravenous (IV) infusion (30 minutes +/- 10 minutes). Bevacizumab infusions will be administered every three weeks for 51 weeks (maximum of 17 infusions) versus standard observation. The following samples will be taken/performed:
1. Venepuncture: blood samples will be taken at each visit, observation arm frequency equivalent to routine clinical care (n = 11), bevacizumab arm frequency higher (n = 33). The volume of blood taken on nine occasions in all will be greater, to collect blood for research purposes
2. Tissue/bodily sample: urinanalysis at baseline in all patients, then at intervals over ten years for patients receiving bevacizumab
3. Biopsy material: excision biopsy of accessible recurrent tumour tissue and adjacent normal tissue from consenting patients
4. Imaging Investigations with radiation: Computed Tomography (CT) (or Magnetic Resonance Imaging [MRI]) scan of head pre-randomisation
5. Day-case attendance: patients receiving bevacizumab will attend an appropriate clinic for drug administration
6. Questionnaire: quality of life questionnaire
Intervention type
Drug
Phase
Phase III
Drug names
Bevacizumab
Primary outcome measure
Overall survival
Secondary outcome measures
1. Disease-free interval
2. Distant metastasis-free interval
3. Quality of life
4. Safety and toxicity
Overall trial start date
05/03/2007
Overall trial end date
05/03/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Written informed consent
2. Age more than or equal to 18 years
3. Able to comply with the protocol
4. Patients with histological confirmation of completely resected American Joint Committee on Cancer (AJCC) stage IIB (T4aN0M0), IIC (T4bN0M0) and III (TxN1-2M0) 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 primary surgery (wide local excision and lymphadenectomy)
7. Eastern Cooperative Oncology Group (ECOG) performance status zero to one
8. Life expectancy more than or equal to six months
9. Adequate haematological function:
a. Absolute Neutrophil Count (ANC) more than or equal to 1.5 x 10^9/L, and
b. platelet count more than or equal to 100 x 10^9/L, and
c. haemoglobin more than or equal to 9 g/dL (may be transfused to maintain or exceed this level)
10. Adequate liver function:
a. total bilirubin less than 1.5 x Upper Limit of Normal (ULN), and
b. Aspartate aminotransferase (AST), and/or Alanine aminotransferase (ALT) less than 2 x ULN
11. Adequate renal function:
a. serum creatinine less than or equal to 1.25 x ULN or calculated creatinine clearance more than or equal to 50 mL/min, and
b. urine dipstick for proteinuria less than 2+. Patients discovered to have more than or equal to 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate less than or equal to 1 g of protein in 24 hours
c. International Normalised Ratio (INR) less than or equal to 1.5 and Partial Prothrombin Time (PPT) less than or equal to 1.5 x ULN
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1320
Participant exclusion criteria
1. Any evidence of distant or non-regional lymph node metastases
2. Evidence of Central Nervous System (CNS) metastases, even if previously treated
3. Incomplete surgical resection of the disease
4. Prior chemotherapy, immunotherapy, hormonal therapy or radiotherapy for melanoma
5. 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
6. Current or recent (within seven days of randomisation) use of aspirin (more than 325 mg/day)
7. Current or recent (within seven days of randomisation) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed
8. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
9. Uncontrolled hypertension (blood pressures: systolic more than 150 mmHg and/or diastolic more than 100 mmHg)
10. Clinically significant (i.e. active) cardiovascular disease for example Coronary Vascular Accident (CVA) (less than or equal to six months before randomisation), myocardial infarction (less than or equal to six months before randomisation), unstable angina, congestive heart failure New York Heart Association (NYHA) class more than or equal to II, serious cardiac arrhythmia requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication
11. Non-healing wound, active peptic ulcer or bone fracture
12. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within six months of randomisation
13. Pregnant or breast-feeding females
14. Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using, or do not agree to use, effective non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) if randomised to the treatment arm and for a period of six months following the last administration of bevacizumab. Men who do not agree to use effective contraception if randomised to the treatment arm and for a period of 60 days following the last administration of bevacizumab
15. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to randomisation
16. Known hypersensitivity to bevacizumab or any of its excipients
17. 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
18. Any condition, which, in the opinion of the investigator, might interfere with the safety of the patient or evaluation of the study objectives
Recruitment start date
05/03/2007
Recruitment end date
05/03/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Organisation
Cambridge University Hospitals NHS Foundation Trust (UK)
Sponsor details
Research and Development Department
Box 146
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (ref: C7535/A6408) (UK)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: https://www.ncbi.nlm.nih.gov/pubmed/24745696
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/29112704