NCT02162563

Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases

Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases CAIRO5 a Randomized Phase 3 Study of the Dutch Colorectal Cancer Group (DCCG)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 530 (actual)
• Sponsor: Dutch Colorectal Cancer Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and no consensus exist on criteria for resectability. In this study colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by an expert panel according to predefined criteria, will be tested for RAS and BRAF tumor mutation status and selected by location of primary tumor. Patients with RAS or BRAF mutant and/or right sided tumors will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab (schedule 1), and triple chemotherapy (FOLFOXIRI) plus bevacizumab (schedule 2). Patients with RAS AND BRAF wildtype AND left-sided primary tumors will be randomized between doublet chemotherapy (FOLFOX or FOLFIRI) plus either bevacizumab (schedule 1) or panitumumab (schedule 3). Patient imaging will be reviewed for resectability by a central panel, consisting of at least one radiologist and three surgeons every assessment. Central panel review will be performed prior to randomization as well as during treatment, as described in the protocol.

Detailed description

Patients will be stratified for resectability of liver metastases (potentially resectable versus permanently unresectable), serum lactate dehydrogenase (LDH) (normal versus abnormal), BRAF mutation status (wildtype versus mutated), type of neoadjuvant chemotherapy (FOLFIRI versus FOLFOX) and hospital of registration. Patients with RAS and BRAF wildtype and left-sided primary tumors will be randomised between FOLFOX or FOLFIRI plus either bevacizumab or panitumumab. The choice between FOLFOX or FOLFIRI is to the discretion of the local investigator, however, the treatment is restricted to regimens that are specified in the protocol. Patients with RAS or BRAF mutated and/or right-sided primary tumors will be randomized between FOLFOX/ FOLFIRI (investigator choice) plus bevacizumab or 5FU, irinotecan, oxaliplatin (FOLFOXIRI) plus bevacizumab. Patients will be evaluated every 8 weeks by CT scan for disease status. The assigned systemic treatment should be continued for at least 6 months or earlier in case of resectability, progression of disease, unacceptable toxicity, or patient refusal. If after 6 months the panel concludes that the patient is still not resectable, it is highly unlikely that resectability will be achieved at all. Therefore the chemotherapy regimen may be reconsidered after 6 months of treatment. These patients should continue with the targeted drug in combination with chemotherapy, but the chemotherapy may be altered into a less toxic schedule such as fluoropyrimidine monotherapy. The targeted drug should be continued until progression or unacceptable toxicity. In patients who will become resectable and undergo secondary surgery of liver metastases, the total duration of preoperative and postoperative treatment together should be 6 months, with the chemotherapy schedule being administered according to the assigned treatment arm. However in these patients the targeted drug (bevacizumab or panitumumab) should not be continued after surgery.

Conditions

• Colorectal Cancer
• Liver Metastases

Interventions

Type	Name	Description
DRUG	FOLFOX/ FOLFIRI with bevacizumab	FOLFIRI + bevacizumab Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by irinotecan 180 mg/m2 i.v. in 60 minutes together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by bolus 5-fluorouracil 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks FOLFOX6 + bevacizumab Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m2 i.v. together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by bolus 5FU 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks
DRUG	FOLFOXIRI with bevacizumab	FOLFOXIRI + bevacizumab Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by irinotecan 165 mg/m2 i.v. in 60 minutes, followed by oxaliplatin 85 mg/m2 i.v. together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 3200 mg/m2 in 46 hours, every 2 weeks
DRUG	FOLFOX/ FOLFIRI with panitumumab	FOLFIRI + panitumumab Panitumumab 6 mg/kg i.v. (1st dose in 60 minutes, if well tolerated subsequent doses in 30 minutes), followed by irinotecan 180 mg/m2 i.v. in 60 minutes together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by bolus 5-fluorouracil 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks FOLFOX6 + panitumumab Panitumumab 6 mg/kg i.v. (1st dose in 60 minutes, if well tolerated subsequent doses in 30 minutes), followed by oxaliplatin 85 mg/m2 i.v. together with leucovorin 400 mg/m2 i.v. in 120 minutes, and bolus 5FU 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks

Timeline

• Start date: 2014-07-01
• Primary completion: 2022-07-01
• Completion: 2025-01-01
• First posted: 2014-06-12
• Last updated: 2025-02-06

Locations

56 sites across 2 countries: Belgium, Netherlands