Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
08_CLPHA_55
Study information
Scientific title
An assessment of imaging and circulating biomarkers in patients with metastatic colorectal carcinoma treated with the anti-vascular endothelial growth factor (anti-VEGF) antibody, bevacizumab
Acronym
TRAVASTIN-1
Study hypothesis
The purpose of the study is to identify biomarkers that can predict clinical benefit in patients treated with bevacizumab and chemotherapy for metastatic colorectal cancer. Our hypotheses are:
1. That a circulating biomarker at baseline or the percentage change in a parameter after single agent treatment will predict benefit in terms of progression-free survival (PFS)
2. That a circulating biomarker will correlate with stable disease or progression on maintenance therapy
3. That bevacizumab improves response rate and PFS in patients with recurrent colorectal cancer who have already been treated with induction and maintenance bevacizumab
Ethics approval
Central Manchester Ethics Committee, 15/06/2009, ref: 09/H1008/99
Study design
Single-centre phase II therapeutic exploratory study
Primary study design
Interventional
Secondary study design
Non randomised study
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
Metastatic colorectal cancer
Intervention
All patients will be treated initially with first line chemotherapy and bevacizumab. They will undergo imaging (dynamic contrast-enhanced magnetic resonance imaging [DCE MRI] and fluorothymidine positron emission tomography [FLT PET]), circulating (circulating endothelial cells, circulating angiomodulatory biomarkers, deoxyribonucleic acid [DNA] analysis) and tissue biomarker investigations.
The treatment will continue until disease progression at which point they will be randomised to receive second line chemotherapy with or without bevacizumab. The treatment will continue until further disease progression.
Intervention type
Drug
Phase
Phase II
Drug names
Bevacizumab
Primary outcome measure
To identify a biomarker or suite of biomarkers that predict clinical benefit in terms of PFS, in patients treated with bevacizumab for metastatic colorectal cancer.
Secondary outcome measures
1. To define biomarker(s) that detect progressive disease in patients treated with bevacizumab-containing regimens for metastatic colorectal cancer
2. To obtain preliminary data on the utility of biomarkers in patients who have been treated with cytotoxic chemotherapy and bevacizumab, followed by maintenance therapy who are then treated, at progression, with chemotherapy with or without bevacizumab
Overall trial start date
01/11/2009
Overall trial end date
01/09/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged greater than or equal to 18 years old, either sex
2. Signed informed consent and ability to comply with study protocol
3. Histologically confirmed colorectal cancer.
4. Previously untreated metastatic disease
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
6. Life expectancy greater than 12 weeks
7. Adequate bone marrow function: absolute neutrophil count (ANC) more than 1.5 x 10^9/L; platelets more than or equal to 100 x 10^9/L; haemoglobin (Hb) more than or equal to 9 g/dL (can be post-transfusion)
8. International normalised ratio (INR) less than or equal to 1.5 and activited partial thromboplastin time (aPTT) less than or equal to 1.5 x upper limit of normal (ULN) within 7 days prior to starting study treatment
9. Adequate liver function: serum bilirubin less than or equal to 1.5 x ULN except in case of known Gilbert syndrome; transaminases less than or equal to 2.5 x ULN in the absence of liver metastases or less than or equal to 5 x ULN in the presence of liver metastases
10. Adequate renal function: estimated glomerular filtration rate greater than or equal to 50 ml/min by the Wright Formula
11. Urine dipstick for proteinuria less than or equal to 2+. If urine dipstick is more than or equal to 2+, a 24-hour urine must demonstrate less than 1 g of protein in 24 hours
12. At least one metastatic deposit in the abdomen (including inguinal lymphadenopathy) liver, retroperitoneum, pelvis or thorax greater than or equal to 3 cm diameter
13. No contraindications to magnetic resonance imaging (MRI) scanning or allergy to gadolininum-containing contrast media
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
70 (out of this, 25 will be entered into the FLT PET protocol)
Participant exclusion criteria
1. Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab
2. Significant traumatic injury or radiotherapy during 4 weeks preceding potential first dose of bevacizumab
3. Adjuvant therapy within the previous 12 months
4. Patients with previous adjuvant exposure to oxaliplatin can only take part if it is more than 12 months since their last exposure to oxaliplatin and they have grade I or less, residual peripheral neuropathy
5. No previous exposure to VEGF inhibitors in the adjuvant setting
6. History or evidence upon physical examination of brain metastases. Evidence of spinal cord compression. Computed tomography (CT)/MRI of the brain is mandatory (within 4 weeks prior to randomisation) in case of clinical evidence of brain metastases.
7. Pregnant or breast-feeding women. Positive pregnancy test (serum or urine beta-human chorionic gonadotropin [ß-HCG]) for women of reproductive potential
8. Fertile woman of childbearing potential not using adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
9. Other malignancies within 5 years prior to randomisation, except for adequately treated carcinoma in situ of the cervix and/or basal cell skin cancer
10. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this trial
11. Known hypersensitivity to bevacizumab, 5-fluorouracil, capecitabine, oxaliplatin or irinotecan
12. Known dihydro-pyrimidine dehydrogenase deficiency
13. Non-healing wound, ulcer or bone fracture
14. Patients cannot enter the trial if they have developed a deep venous thrombosis (DVT) or commenced therapeutic anticoagulation for any other reason, e.g., atrial fibrillation (AF) within the 4 weeks preceding the trial. Patients with a known DVT or AF on stable therapeutic doses of low molecular weight heparin for greater than 4 weeks duration, can enter the trial.
15. Patients with haemorrhagic disorders
16. Poorly controlled hypertension (sustained blood pressure [BP] greater than 150/100 mmHg despite antihypertensive therapy
17. Previous cerebrovascular accident (CVA), transient ischaemic attack (TIA) or subarachnoid haemorrhage (SAH) within six months before trial entry
18. Clinically significant cardiovascular disease, for example:
18.1. Myocardial infarction or unstable angina within 6 months of trial entry
18.2. New York Heart Association (NYHA) grade 2 or worse congestive heart failure (CHF)
18.3. Poorly controlled cardiac arrhythmia despite medication
19. Current or recent (within 10 days prior to first dose of trial treatment) use of aspirin greater than or equal to 325 mg/day
20. Pre-existing sensory or motor neuropathy greater than or equal to grade 2, uncontrolled spinal cord compression, or
21. Carcinomatous meningitis or new evidence of brain or leptomeningeal disease
22. Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline of greater than 3 loose stools daily
23. Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhoea, unresolved bowel obstruction/sub-obstruction, extensive small intestine resection with chronic diarrhoea
24. History of anaphylaxis or known intolerance to atropine sulphate or loperamide or appropriate antiemetics to be administered in conjunction with chemotherapy
25. Patients with a colonic stent
26. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
Recruitment start date
01/11/2009
Recruitment end date
01/09/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Christie NHS Foundation Trust
Manchester
M20 4BX
United Kingdom
Sponsor information
Organisation
The Christie NHS Foundation Trust (UK)
Sponsor details
Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Industry
Funder name
Roche
Alternative name(s)
F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Switzerland
Results and Publications
Publication and dissemination plan
The manuscript will be submitted to a journal for publication by December 2016.
IPD sharing plan
Patient data will be anonymised and will be provided as subject number and as data in the manuscript.
Intention to publish date
31/12/2016
Participant level data
Other
Basic results (scientific)
Publication list