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

ISRCTN	ISRCTN81261306
DOI	https://doi.org/10.1186/ISRCTN81261306
EudraCT/CTIS number	2006-005505-64
Secondary identifying numbers	2006-005505-64

Submission date: 03/01/2007
Registration date: 30/03/2007
Last edited: 26/10/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-bevacizumab-after-surgery-for-melanoma-skin-cancer

Contact information

Dr Philippa Corrie
Scientific

Oncology Centre
Box 193
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Phone	+44 (0)1223 216083
Email	pippa.corrie@addenbrookes.nhs.uk

Study information

Study design	Randomised phase III multi-centre prospective clinical trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
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
Study acronym	AVAST-M
Study objectives	To determine the overall survival of patients treated with bevacizumab, compared with standard observation after resection of high risk melanoma.
Ethics approval(s)	Oxford C Multi-centre Research Ethics Committee, ref: 07/Q1606/15 - approval pending
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	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 study start date	05/03/2007
Completion date	05/03/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1320
Key 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
Key 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
Date of first enrolment	05/03/2007
Date of final enrolment	05/03/2017

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Addenbrooke's Hospital

Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Research and Development Department
Box 146
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Website	http://www.addenbrookes.org.uk/
"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Charity

Cancer Research UK (ref: C7535/A6408) (UK)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Plain English results			No	Yes
Results article	results	01/05/2014	Yes	No
Results article	results	01/02/2018	Yes	No

Editorial Notes

26/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
08/11/2017: Publication references added.