Second-line FOLFOX With or Without Regorafenib in mCRC Patients Failed to First-line Irinotecan Plus Fluoropyrimidines

Metastatic Colorectal Cancer Clinical Trial

Official title: Randomized Phase III Study of Oxaliplatin, Fluorouracil and Leucovorin (FOLFOX) With or Without Regorafenib in Patients With Metastatic Colorectal Cancer Progressed After First-line Irinotecan Plus Fluoropyrimidines

Status Withdrawn

Clinical Trial Summary

Regorafenib has been proved to improved survival in patients with metastatic colorectal cancer who have been failed to all of known standard chemotherapy (The CORRECT study). The phase Ib study of regorafenib plus FOLFOX or FOLFIRI was performed and the dose of regorafenib was fixed; 160 mg/day on days 4 to 10 (7 days per cycle when combined with FOLFOX or FOLFIRI). Regorafenib plus FOLFOX as second-line chemotherapy in mCRC patients who progressed after first-line irinotecan-based chemotherapy has not been studied yet, and because there have been unmet needs for the discovery of valid targeted agent combination for the second-line FOLFOX as above reasons, the investigators planned this study of regorafenib plus FOLFOX as second-line chemotherapy in mCRC patients who progressed after first-line irinotecan-based chemotherapy.

Clinical Trial Description

Limited active drugs are available for the treatment of patients with metastatic colorectal cancer (mCRC) at present and upfront doublet combination of fluoropyrimidines plus either oxaliplatin or irinotecan is regarded as reference strategy for patients appropriate for intensive therapy. Before the era of targeted agents, the treatment strategies in terms of either combination or sequence of cytotoxic agents were rather simple; survival outcomes did not differ according to either the administration sequence of oxaliplatin or irinotecan, or the sequential versus combination chemotherapy in the treatment continuum. However, the treatment strategies have become more complicated in the era of targeted agents.

In case of failure to first-line oxaliplatin plus fluoropyrimidines (FOLFOX or CapeOX) with or without bevacizumab, second-line chemotherapy with FOLFIRI would be administered for treatment continuum, and more various targeted agents can be combined in these setting; bevacizumab beyond progression only in patients who have been treated with first-line bevacizumab plus FOLFOX or CapeOX (TML and BRiTE), cetuximab (only for patients with wild-type KRAS), panitumumab (only for patients with wild-type KRAS), and aflibercept (VELOUR). However, there have been a few valid targeted agents which could be combined in the second line FOLFOX or CapeOX in those progressed after first-line FOLFIRI with or without targeted agents; bevacizumab beyond progression could be a valid treatment strategy only in those received first-line bevacizumab plus FOLFIRI. Higher dose of bevacizumab (10 mg/kg/2-week) could be combined to FOLFOX as second-line chemotherapy; however, it is not recommended at present in terms of cost effectiveness and higher adverse events, and cetuximab plus oxaliplatin-based chemotherapy is neither recommended by current consensus. Thus, there have been unmet needs for the discovery of valid targeted agent combination for the second-line FOLFOX as above reasons. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

• NCT number: NCT01786538
• Study type: Interventional
• Source: Asan Medical Center
• Status: Withdrawn
• Phase: Phase 3
• Start date: June 2013
• Completion date: May 2017