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Rectal CancerPhase 2BACCHUSNCT01650428

Bevacizumab And Combination Chemotherapy in Rectal Cancer Until Surgery

A Phase 2 study testing Bevacizumab, Irinotecan and Oxaliplatin in people with Rectal Cancer, run by University College, London at 11 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Rectal Cancer
What is being tested?
Bevacizumab, Irinotecan and Oxaliplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
11 sitesUnited Kingdom
Study dates
Apr 2013to 14 Feb 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • ANC ≥2 x 109/L
  • Platelet count ≥100 x 109/L
  • ALT or AST ≤1.5 x ULN (upper limit of normal)
  • ALP ≤1.5 x ULN
  • Total bilirubin ≤1.5 x ULN
  • Serum creatinine ≤1.5 x ULN
  • Creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula
  • INR ≤ 1.1
  • Urine protein ≤1+ with dipstick or urine analysis
  • For proteinuria ≥2+ or urine protein/creatinine ratio ≥ 1.0, 24-h urine protein should be obtained and the level must be ≤2 g for eligibility
  • No evidence of established or acute ischaemic heart disease on ECG and normal clinical cardiovascular assessment
  • No known significant impairment of intestinal absorption
  • At least 18 years of age, but not more than 75 years
  • Willing and able to give informed consent, comply with treatment and follow up schedule

Who cannot join

  • 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
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  • 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
  • Previous intolerance to fluoropyrimidine chemotherapy
  • Previous treatment with bisphosphonates
  • Infectious illness requiring antibiotics within 1 week of randomisation
  • Previous treatment with another investigational agent within 30 days prior to randomisation
  • Patients with a history of previous malignancy in the past 5 years, excepting basocellular or squamous cell skin cancer, or properly treated cervicouterine cancer in situ
  • Known HIV, HBV or HCV infection
  • Current smoker, or clinically relevant history of drug or alcohol abuse
  • Pregnant or lactating women or pre menopausal women not using adequate contraception. Men and women of child-bearing potential must use adequate contraception
  • Patients with any other condition or concurrent medical or psychiatric disease who, in the opinion of the investigator, is not eligible to enter the study
  • Inability or unwillingness to comply with the protocol

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United Kingdom11 sites

  • Blackpool Victoria Hospital

    Blackpool

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Charing Cross Hospital

    London

  • Guy's and St Thomas' Hospital

    London

  • Hammersmith Hospital

    London

  • North MiddlesexHospital

    London

  • Royal Marsden Hospitals NHS Foundation Trust

    London

  • UCLH

    London

  • Mount Vernon Hospital

    Middlesex

  • Wexham Park Hospital

    Slough

  • Lister Hospital

    Stevenage

Other trials in United Kingdom

About this study

Official title: A Phase II, Multicentre, Open-Label, Randomised Study of Neoadjuvant Chemotherapy and Bevacizumab in Patients With MRI Defined High-Risk Cancer of the Rectum

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.

Read the detailed description

The purpose of this study is to look at two different combinations of anticancer drugs to see how effective they are at shrinking your cancer and preventing it from coming back after surgery. Patients with locally advanced rectal cancer are sometimes treated with radiotherapy, with or without chemotherapy, before having surgery. Radiotherapy treats only the main tumour in the rectum. This means that if tiny deposits of cancer have spread to other parts of the body (metastases), these could continue to grow. Giving chemotherapy and radiotherapy together (chemoradiotherapy) can treat both the main tumour and any spread. However, due to the side-effects we can't give as much chemotherapy in combination with radiotherapy than if chemotherapy were given on its own and treatment of possible metastases may not be as good as it could be. If the risk of the main tumour coming back is quite small, then giving treatment that targets metastases should be the best option.

This study looks at two well known combinations of chemotherapy drugs: FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan). Chemotherapy works by killing cancer cells. In addition, the anticancer drug bevacizumab will be given with both the FOLFOX and FOLFOXIRI. Bevacizumab is an "anti-angiogenesis" drug. It works by stopping tumours from making new blood vessels. Without new blood vessels, the cancer cells do not get the food and oxygen they need to survive and grow. Attacking the cancer in these ways may be more effective than chemotherapy alone.

Conditions
Rectal Cancer
Keywords
Rectal Cancer, Bevacizumab, Neoadjuvant, Chemotherapy, Randomised
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Avastin

    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).

  • IrinotecanDrug

    Also called Campto

    165 mg/m2 IV (intravenous) over 1 hour on day 1 of two weekly cycle. Number of cycles: 1-6

  • OxaliplatinDrug

    Also called Eloxatin

    165 mg/m2 IV (intravenous) over 1 hour on day 1 of two weekly cycle. Number of cycles: 1-6

  • 5-FluorouracilDrug

    Also called 5-FU

    3200 mg/m2 IV (intravenous), continuous infusion over 48 hours starting on day 1 of two weekly cycle. Number of cycles: 1-6

Study groups in NCT01650428
Study groupRoleWhat they receive
FOLFOX & BevacizumabExperimentalBevacizumab - 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)
Receives: Biological: Bevacizumab; Drug: Oxaliplatin; Drug: 5-Fluorouracil
FOLFOXIRI & BevacizumabExperimentalBevacizumab - 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)
Receives: Biological: Bevacizumab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-Fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  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%).

    Measured: The pCR rate will be assessed after surgery, therefore approximately 24 weeks after randomisation.

Secondary outcomes (12)

  1. RECIST Response Rate

    Complete response and Partial response will be considered as responses.

    Measured: This will be assessed after chemotherapy has ended. Chemotherapy will be given for up to 12 weeks.

  2. CRM Negative Resection Rate

    Those with a resection distance >1mm amongst those having surgery.

    Measured: This will be assessed after surgery, therefore approximately 24 weeks after randomisation.

  3. T and N stage downstaging

    This will examine T and N stage to assess whether stage has worsened from baseline to post-treatment. A patient will be considered to have downstaged if i) both T and N stage decrease; ii) either T or N stage decreases and the other remains stable.

    Measured: This will be assessed at the completion of treatment. Treatment will be given for up to 12 weeks.

  4. Progression Free Survival

    This is defined as time from randomisation to disease progression or death, whichever occurs first. Disease progression will be assessed by the RECIST criteria at pre-cycle 4 and post-treatment.

    Measured: This will be assessed pre-cycle 4 and post-treatment, therefore at 6 weeks and 12 weeks after randomisation.

  5. Disease Free Survival

    This is defined as the time from surgery with complete resections (R0) to the occurrence of relapse, second colorectal primary or death from any cause, whichever occurs first. Only subjects who have a complete resection (R0) will be included in this analysis. Patients who are alive, without recurrence and with no secondary colorectal cancer at the time of cut-off will be right-censored at the most recent date of assessment.

    Measured: 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.

  6. Overall Survival

    This is defined as the time from study entry until death. The OS of all subjects and of the subgroup who had complete resection (R0) will be calculated.

    Measured: From study entry until death, until 3 years after randomisation.

  7. Local Control

    This will be assessed just for those patients who attain a CRM negative resection.

    Measured: From date of surgery until local failure, until 3 years after randomisation.

  8. 1 year Colostomy Rate

    This will be assessed post-surgery. The Kaplan-Meier estimate will be used to estimate the colostomy rate at 1 year.

    Measured: Post surgery (approximately 24 weeks after randomisation) and 1 year after randomisation.

  9. Frequency and severity of Adverse Events

    This will be tabulated for both treatment arms, including all grade 1-5 toxicities.

    Measured: This will be from date of randomisation until 30 days after completion of treatment. Treatment is given for up to 12 weeks.

  10. Compliance of Chemotherapy

    Dose reductions and dose delays to all chemotherapy agents will be recorded.

    Measured: This will be at the end of treatment (up to 12 weeks)

  11. Tumour Regression Grade (TRG)

    This results from post-resection tumour sample will be used to categorise TRG into five groups using Dworak method.

    Measured: Assessed after surgery, approximately 24 weeks after randomisation.

  12. Tumour Cell Density

    This results from post-resection tumour sample will be used to provide an estimate of the average TCD and its 95% CI. This may be expressed as a mean, or if the date is skewed, the median.

    Measured: This will be assessed after surgery, approximately 24 weeks after randomisation.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2012 (estimated)
  2. Study startApr 2013
  3. Primary completion10 Jan 2018
  4. Study completion14 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01650428
Sponsor's protocol ID
UCL/09/0176
Acronym
BACCHUS
Status last verified
Oct 2018
First submitted
16 Jul 2012
Last updated
7 Oct 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26493588

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Irinotecan and Oxaliplatin in people with Rectal Cancer, run by University College, London at 11 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Complete Response (PCR) (time frame: The pCR rate will be assessed after surgery, therefore approximately 24 weeks after randomisation.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01650428, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2019.

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