Bevacizumab And Combination Chemotherapy in Rectal Cancer Until Surgery
BACCHUS
A Phase II, Multicentre, Open-Label, Randomised Study of Neoadjuvant Chemotherapy and Bevacizumab in Patients With MRI Defined High-Risk Cancer of the Rectum
1 other identifier
interventional
20
1 country
11
Brief Summary
The purpose of this study is to evaluate the efficacy, toxicity and feasibility of FOLFOX/ bevacizumab and FOLFOXIRI/ bevacizumab neoadjuvant therapy in poor prognosis rectal cancer as defined by MRI.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Apr 2013
Longer than P75 for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 16, 2012
CompletedFirst Posted
Study publicly available on registry
July 26, 2012
CompletedStudy Start
First participant enrolled
April 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 10, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 14, 2019
CompletedOctober 7, 2019
October 1, 2018
4.8 years
July 16, 2012
October 3, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Pathological Complete Response (PCR)
The proportion of patients in each arm who achieve a pCR will be presented, along with a 95% CI. Within each group the achieved pCR rate will be compared to the rate achieved by radiotherapy alone (5%).
The pCR rate will be assessed after surgery, therefore approximately 24 weeks after randomisation.
Secondary Outcomes (12)
RECIST Response Rate
This will be assessed after chemotherapy has ended. Chemotherapy will be given for up to 12 weeks.
CRM Negative Resection Rate
This will be assessed after surgery, therefore approximately 24 weeks after randomisation.
T and N stage downstaging
This will be assessed at the completion of treatment. Treatment will be given for up to 12 weeks.
Progression Free Survival
This will be assessed pre-cycle 4 and post-treatment, therefore at 6 weeks and 12 weeks after randomisation.
Disease Free Survival
This will be length of time from date of surgery till relapse, second colorectal primary or death from any cause, whichever occurs first. These occurrences will be reported on CRFs every six months for up to three years.
- +7 more secondary outcomes
Study Arms (2)
FOLFOX & Bevacizumab
EXPERIMENTALBevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour. Treatment given every 2 weeks for 12 weeks (for 6 cycles)
FOLFOXIRI & Bevacizumab
EXPERIMENTALBevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Irinotecan - 165 mg/m2 IV over 1 hour, Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour. Treatment given every 2 weeks for 12 weeks (for 6 cycles)
Interventions
5 mg/kg, IV (in the vein) over 30-90 minutes, on day 1 of each 2 weekly cycles. Number of cycles: 1-5 (bevacizumab should not be administered during cycle 6).
165 mg/m2 IV (intravenous) over 1 hour on day 1 of two weekly cycle. Number of cycles: 1-6
165 mg/m2 IV (intravenous) over 1 hour on day 1 of two weekly cycle. Number of cycles: 1-6
3200 mg/m2 IV (intravenous), continuous infusion over 48 hours starting on day 1 of two weekly cycle. Number of cycles: 1-6
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of adenocarcinoma of the rectum
- Distal part of the tumour within 4-12 cm of the anal verge
- No unequivocal evidence of established metastatic disease (on chest/abdominal/pelvis CT).Patients with equivocal lesions (as determined at MDT) are eligible
- MRI-evaluated locally advanced tumour with the following:
- T3 tumours extending (≥ 4 mm), beyond the muscularis propria N0-N2
- Or tumours (involving or threatening the peritoneal surface)
- OR presence of macroscopic extramural venous invasion (V2 disease)
- AND for tumours below the peritoneal reflection, the primary tumour or involved lymph node (on MRI) must be \>1 mm from the mesorectal fascia
- Measurable disease (using RECIST criteria v1.1)
- WHO performance status 0 - 1
- In the opinion of the investigator:
- General condition considered suitable for radical pelvic surgery
- Candidate for systemic therapy with FOLFOX/FOLFOXIRI plus bevacizumab
- Adequate bone marrow, hepatic and renal function:
- Haemoglobin ≥80 g/L
- +14 more criteria
You may not qualify if:
- Disease outside of the mesorectal envelope (internal iliac/lateral pelvic lymph node)
- Clinically significant cardiovascular or coronary disease \<2 years before randomisation
- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
- History of an arterial thromboembolic event during the previous 2 years
- Evidence of bleeding problems or coagulopathy
- Significant and continuing rectal bleeding leading to a haemoglobin \<8 g/dL
- Patients receiving warfarin/coumarin derived anticoagulants at full therapeutic doses are excluded, but prophylactic doses of 1mg to prevent Hickman line clotting are eligible
- Chronic use of aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day) within 10 days of first planned study treatment
- Require regular use of anti-diarrhoeal (e.g. daily use of loperamide)
- Serious uncontrolled intercurrent illness including poorly controlled diabetes mellitus
- Known hypersensitivity to any of the study drugs
- Serious wound, ulcer or bone fracture
- Current or impending rectal obstruction
- Metallic colonic or rectal stent in situ
- Previous pelvic radiotherapy
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Cancer Research UKcollaborator
- Hoffmann-La Rochecollaborator
Study Sites (11)
Blackpool Victoria Hospital
Blackpool, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Charing Cross Hospital
London, United Kingdom
Guy's and St Thomas' Hospital
London, United Kingdom
Hammersmith Hospital
London, United Kingdom
North MiddlesexHospital
London, United Kingdom
Royal Marsden Hospitals NHS Foundation Trust
London, United Kingdom
UCLH
London, United Kingdom
Mount Vernon Hospital
Middlesex, United Kingdom
Wexham Park Hospital
Slough, United Kingdom
Lister Hospital
Stevenage, United Kingdom
Related Publications (1)
Glynne-Jones R, Hava N, Goh V, Bosompem S, Bridgewater J, Chau I, Gaya A, Wasan H, Moran B, Melcher L, MacDonald A, Osborne M, Beare S, Jitlal M, Lopes A, Hall M, West N, Quirke P, Wong WL, Harrison M; Bacchus investigators. Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum. BMC Cancer. 2015 Oct 23;15:764. doi: 10.1186/s12885-015-1764-1.
PMID: 26493588DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rob Glynne-Jones, BA MB FRCP FRCR
Mount Vernon Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 16, 2012
First Posted
July 26, 2012
Study Start
April 1, 2013
Primary Completion
January 10, 2018
Study Completion
February 14, 2019
Last Updated
October 7, 2019
Record last verified: 2018-10