Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma (CAIRO3)
The optimal duration of systemic treatment in patients with advanced colorectal cancer is unknown.
In this study the effects of bevacizumab and low-dose continuous chemotherapy with capecitabine is investigated in patients who have responded to 6 courses of oxaliplatin, capecitabine and bevacizumab ("induction treatment", at standard doses). This treatment is continued until progression or severe toxicity. This regimen is compared to the effects a observation without treatment after the induction treatment.
In case of disease progression, induction treatment will be reintroduced.
Colorectal Cancer Metastatic
Drug: capecitabine + bevacizumab
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Maintenance Treatment With Capecitabine and Bevacizumab Versus Observation After Induction Treatment With Chemotherapy and Bevacizumab as First-line Treatment in Patients With Advanced Colorectal Carcinoma|
- Progression-free survival after re-introduction of MTD chemotherapy and bevacizumab (PFS2) [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Progression-free survival between observation versus maintenance therapy (PFS1) [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Response rate during re-introduction of MTD chemotherapy and bevacizumab [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
- Quality of life [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: study duration ] [ Designated as safety issue: No ]
- Translational research [ Time Frame: study duration ] [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
observation after induction treatment
Active Comparator: 2
capecitabine plus bevacizumab
Drug: capecitabine + bevacizumab
Ca 1250 mg/m2 daily orally continuously, B 7.5 mg/kg i.v. q 3 w
Standard 1st-line treatment for patients with advanced colorectal cancer currently consists of chemotherapy plus bevacizumab. With this approach the median overall survival is approximately 20 months, and progression-free survival in first-line approximately 9-11 months. The optimal duration of treatment is unknown. Current data suggest that the efficacy of bevacizumab is dependent on concomitant use of chemotherapy. However, oxaliplatin almost invariably gives rise to neuropathy after 6-8 cycles. Prolonged use of capecitabine is associated with e.g. hand-foot syndrome. Lastly, the prolonged use of these agents is associated with considerable costs.
Evidence, mainly preclinical, suggests that continuous dosing metronomic chemotherapy may be more efficacious than interval-chemotherapy given at MTD. In this study the concept of metronomic chemotherapy is explored by administering a continuous daily instead of the usual 2 weeks-on/1 week-off oral dosing regimen of low-dose capecitabine plus bevacizumab as maintenance therapy after induction combination chemotherapy given at MTD plus bevacizumab.
|University Medical Center Nijmegen|
|Nijmegen, Gelderland, Netherlands|
|Principal Investigator:||C. JA Punt, MD PhD||Amsterdam Medical Centre, Amsterdam Netherlands|