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

ISRCTN ISRCTN97323814
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

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

Study designSingle-centre phase II therapeutic exploratory study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleAn 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 acronymTRAVASTIN-1
Study objectivesThe 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) studiedMetastatic colorectal cancer
InterventionAll 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Bevacizumab
Primary outcome measureTo 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 measures1. 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 date01/11/2009
Completion date01/09/2016

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants70 (out of this, 25 will be entered into the FLT PET protocol)
Key inclusion criteria1. 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 criteria1. 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 enrolment01/11/2009
Date of final enrolment01/09/2015

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

The Christie NHS Foundation Trust
Manchester
M20 4BX
United Kingdom

Sponsor information

The Christie NHS Foundation Trust (UK)
Hospital/treatment centre

Wilmslow Road
Withington
Manchester
M20 4BX
England
United Kingdom

Website http://www.christie.nhs.uk/
ROR logo "ROR" https://ror.org/03v9efr22

Funders

Funder type

Industry

Roche
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 date31/12/2016
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planThe manuscript will be submitted to a journal for publication by December 2016.
IPD sharing planPatient 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
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.