A Phase II Study of Bevacizumab, Irinotecan and Capecitabine in Patients With Previously Untreated Metastatic Colorectal Cancer
Bevacizumab has recently been shown to improve survival when combined with chemotherapy in patients with previously untreated metastatic colorectal cancer. Bevacizumab is usually given together with infusional 5-FU, which requires a central line. A central line is inconvenient for patients, and may increase risk of infection, and thrombosis. Furthermore, a central line increases resource demands for interventional radiology, chemo daycare. Capecitabine is administered orally, and converted to 5-FU intracellularly. Chronic administration of capecitabine mimics infusional 5-FU. This study is designed to evaluate whether the combination of irinotecan, capecitabine and bevacizumab is effective as a first-line therapy for patients with metastatic colorectal cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Bevacizumab, Irinotecan and Capecitabine in Patients With Previously Untreated Metastatic Colorectal Cancer|
- To determine the objective response rate (ie. the rate of partial response plus complete response as defined by RECIST criteria) of irinotecan, capecitabine and bevacizumab (XELIRI-A) in patients with previously untreated metastatic colorectal cancer. [ Time Frame: Radiological evaluation every 9 weeks, with confirmatory scans 4 weeks after objective response ] [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
- hydrochloride trihydrate
The FOLFIRI regimen has become the standard 1st line therapy for metastatic colorectal cancer in Canada. This regimen consists of irinotecan in combination with bolus 5-FU/leucovorin, followed by 46-hour infusional 5-FU every 2 weeks. It requires a central line and an infusion pump for delivering 5-FU, and necessitates at least 2 visits to the chemotherapy units every 2 weeks, which not only incurs additional cost and inconvenience to patients, but also increases the risk of complications such as thrombosis and infection due to the central line. In addition, due to resources limitations, patients often have to wait several weeks for central line placement. The XELIRI (irinotecan and capecitabine) regimen has been in use at the Princess Margaret Hospital (PMH) as the first-line treatment of patients with metastatic colorectal cancer since May, 2003. The choice of XELIRI over FOLFIRI was made in efforts to reduce demands on resources, enable patients to start therapy sooner, increase patient convenience and potentially reduce complications associated with central venous access. The regimen consists of irinotecan 250 mg/m2 IV on day 1 and capecitabine 1000 mg/m2 PO BID from days 1-14 every 3 weeks. The dose was reduced to irinotecan 200 mg/m2 on day 1 and capecitabine 750 mg/m2 in patients > 65 years old or in patients with renal impairment. So far, 101 patients have been treated on this regimen at PMH. Among 76 patients evaluable for response, there have been 34 confirmed partial responses (44.7%) and a further 18 patients with stable disease (23.7%), for a disease control rate of 68.4%. Furthermore, this regimen was well tolerated with main side effects being diarrhea and neutropenia. With availability of bevacizumab, 12 patients were treated with the XELIRI regimen in combination with bevacizumab at PMH as part of the BEAT (Bevcizumab Expanded Access Trial ) study up to October, 2005. Of 10 patients who were treated with 3 or more cycles of chemotherapy, there were 7 confirmed partial responses and 2 additional patients with stable disease. One patient with non-measurable but evaluable disease had marked reduction in infiltration in the sacrum. There were no instances of GI perforation, febrile neutropenia, or toxic death. The median number of cycles of treatment was 6, and 9 of 12 patients are still receiving treatment. There were, however, a total of 8 dose reductions of capecitabine in 6 patients, with majority of dose reductions as a result of hand-foot syndrome. Although these efficacy and toxicity data are extremely encouraging, the small number of patients limits the potential application of these data.Because of the encouraging preliminary results, it is necessary to conduct a prospective clinical study to further evaluate the efficacy and toxicity of irinotecan, capecitabine and bevacizumab combination (the XELIRI-A regimen) as first-line chemotherapy for patients with advanced colorectal cancer. Results from this study would provide the scientific basis for a randomized phase III study to compare the XELIRI-A regimen to the IFL (FOLFIRI) + bevacizumab regimen. Furthermore, it will have practical implications for our centre. Compared to infusional or bolus 5-FU based regimens, the XELIRI-A regimen will reduce workload in the chemotherapy daycare unit and drug costs, reduce demands for resources such as infusion pumps and interventional radiology time, enable patients to start therapy sooner, and improve patient convenience.
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Eric Chen||Princess Margaret Hospital, University Health Network|