Bevacizumab And Combination Chemotherapy in Rectal Cancer Until Surgery
- Conditions
- Rectal Cancer
- Interventions
- Registration Number
- NCT01650428
- Lead Sponsor
- University College, London
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FOLFOXIRI & Bevacizumab Bevacizumab Bevacizumab - 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) FOLFOX & Bevacizumab Bevacizumab Bevacizumab - 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) FOLFOX & Bevacizumab Oxaliplatin Bevacizumab - 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) FOLFOX & Bevacizumab 5-Fluorouracil Bevacizumab - 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 Irinotecan Bevacizumab - 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) FOLFOXIRI & Bevacizumab Oxaliplatin Bevacizumab - 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) FOLFOXIRI & Bevacizumab 5-Fluorouracil Bevacizumab - 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)
- Primary Outcome Measures
Name Time Method Pathological Complete Response (PCR) The pCR rate will be assessed after surgery, therefore approximately 24 weeks after randomisation. 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%).
- Secondary Outcome Measures
Name Time Method T and N stage downstaging This will be assessed at the completion of treatment. Treatment will be given for up to 12 weeks. 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.
Local Control From date of surgery until local failure, until 3 years after randomisation. This will be assessed just for those patients who attain a CRM negative resection.
Tumour Regression Grade (TRG) Assessed after surgery, approximately 24 weeks after randomisation. This results from post-resection tumour sample will be used to categorise TRG into five groups using Dworak method.
Overall Survival From study entry until death, until 3 years after randomisation. 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.
1 year Colostomy Rate Post surgery (approximately 24 weeks after randomisation) and 1 year after randomisation. This will be assessed post-surgery. The Kaplan-Meier estimate will be used to estimate the colostomy rate at 1 year.
Frequency and severity of Adverse Events This will be from date of randomisation until 30 days after completion of treatment. Treatment is given for up to 12 weeks. This will be tabulated for both treatment arms, including all grade 1-5 toxicities.
RECIST Response Rate This will be assessed after chemotherapy has ended. Chemotherapy will be given for up to 12 weeks. Complete response and Partial response will be considered as responses.
Compliance of Chemotherapy This will be at the end of treatment (up to 12 weeks) Dose reductions and dose delays to all chemotherapy agents will be recorded.
CRM Negative Resection Rate This will be assessed after surgery, therefore approximately 24 weeks after randomisation. Those with a resection distance \>1mm amongst those having surgery.
Progression Free Survival This will be assessed pre-cycle 4 and post-treatment, therefore at 6 weeks and 12 weeks after randomisation. 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.
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. 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.
Tumour Cell Density This will be assessed after surgery, approximately 24 weeks after randomisation. 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.
Trial Locations
- Locations (11)
Wexham Park Hospital
🇬🇧Slough, United Kingdom
UCLH
🇬🇧London, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Royal Marsden Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Guy's and St Thomas' Hospital
🇬🇧London, United Kingdom
Mount Vernon Hospital
🇬🇧Middlesex, United Kingdom
North MiddlesexHospital
🇬🇧London, United Kingdom
Lister Hospital
🇬🇧Stevenage, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom