Condition category
Cancer
Date applied
03/01/2007
Date assigned
30/03/2007
Last edited
15/12/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

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

Approval pending from the Oxford C Multi-centre Research Ethics Committee (ref: 07/Q1606/15).

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

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 (Avastin®)

Primary outcome measures

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

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

Oncology Centre
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

http://www.addenbrookes.org.uk/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes