Identifying biomarkers to predict clinical benefit in patients with colorectal cancer treated with bevacizumab
ISRCTN | ISRCTN97323814 |
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DOI | https://doi.org/10.1186/ISRCTN97323814 |
Secondary identifying numbers | 08_CLPHA_55 |
- 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
Contact information
Prof Gordon Jayson
Scientific
Scientific
Consultant Medical Oncologist
The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Study information
Study design | Single-centre phase II therapeutic exploratory study |
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Primary study design | Interventional |
Secondary study design | Non randomised study |
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 | 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 |
Pharmaceutical study type(s) | |
Phase | Phase II |
Drug / device / biological / vaccine name(s) | 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 study start date | 01/11/2009 |
Completion date | 01/09/2016 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Lower age limit | 18 Years |
Sex | Both |
Target number of participants | 70 (out of this, 25 will be entered into the FLT PET protocol) |
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
- England
- United Kingdom
Study participating centre
The Christie NHS Foundation Trust
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
Sponsor information
The Christie NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Wilmslow Road
Withington
Manchester
M20 4BX
England
United Kingdom
Website | http://www.christie.nhs.uk/ |
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https://ror.org/03v9efr22 |
Funders
Funder type
Industry
Roche
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG, Roche Holding AG, Roche Holding Ltd, Roche Holding, Roche Holding A.G., Roche Holding, Limited, F. Hoffmann-La Roche & Co.
- Location
- Switzerland
Results and Publications
Intention to publish date | 31/12/2016 |
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Individual participant data (IPD) Intention to share | Yes |
IPD sharing plan summary | Other |
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. |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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Results article | results | 07/11/2018 | 31/01/2019 | Yes | No |
Plain English results | 04/07/2019 | No | Yes | ||
HRA research summary | 28/06/2023 | No | No |
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.