Identifying biomarkers to predict clinical benefit in patients with colorectal cancer treated with bevacizumab

ISRCTN	ISRCTN97323814
DOI	https://doi.org/10.1186/ISRCTN97323814
Protocol serial number	08_CLPHA_55
Sponsor	The Christie NHS Foundation Trust (UK)
Funder	Roche

Submission date: 19/01/2010
Registration date: 31/08/2010
Last edited: 04/07/2019

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-new-types-of-mri-scans-see-how-chemotherapy-affects-bowel-cancer-cells

Contact information

Prof Gordon Jayson
Scientific

Consultant Medical Oncologist
The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Study information

Primary study design	Interventional
Study design	Single-centre phase II therapeutic exploratory study
Secondary study design	Non randomised study
Study type	Participant information sheet
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
Study acronym	TRAVASTIN-1
Study objectives	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(s)	Central Manchester Ethics Committee, 15/06/2009, ref: 09/H1008/99
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Bevacizumab
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	01/09/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	70
Key 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
Key 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
Date of first enrolment	01/11/2009
Date of final enrolment	01/09/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

The Christie NHS Foundation Trust

Manchester
M20 4BX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan	Patient data will be anonymised and will be provided as subject number and as data in the manuscript.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	07/11/2018	31/01/2019	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			04/07/2019	No	Yes

Editorial Notes

04/07/2019: Cancer Research UK results link added to the results (plain English) field.
31/01/2019: Publication reference added
03/01/2017: The overall trial end date was changed from 01/06/2014 to 01/09/2016.