NCT03641976

A Study of Bevacizumab, Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (A-FOLFOXIRI) Compared With Bevacizumab, Infusional Fluorouracil, Leucovorin, and Irinotecan/Oxaliplatin (A-FOLFIRI/FOLFOX) as First-line Treatment for Metastatic Right-sided Colon Cancer

A Randomized, Open-label, Multicenter Phase II Study of Bevacizumab, Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (A-FOLFOXIRI) Compared With Bevacizumab, Infusional Fluorouracil, Leucovorin, and Irinotecan/Oxaliplatin (A-FOLFIRI/FOLFOX) as First-line Treatment for Metastatic Right-sided Colon Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Yonsei University · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Recently, the importance of prognosis according to the location of the primary tumor in colorectal cancer has been raised. In the CALGB / SWOG 80405 study published in 2016, the addition of bevacizumab or cetuximab to the first line FOLFIRI / FOLFOX in KRAS (codon 12, 13) wild type metastatic colorectal cancer (mCRC) patients did not show a significant difference between overall survival (OS) and progression free survival (PFS) in both groups. Alan P. Venook et al. published a follow-up subgroup analysis on the effect of primary tumor location at 2016 ASCO. In the treatment group with cetuximab, the difference in treatment effect was significant according to the primary tumor location. The right colon cancer showed a poor prognosis for cetuximab treatment. (PFS: 7.8 vs 12.4 months, HR 1.56, p \<0.0001 / OS: 16.7 vs 36.0months, HR 1.87, P \<0.0001). Therefore, the investigators propose a phase II trial for the efficacy evaluation of bevacizumab-FOLFOXIRI and bevacizumab-FOLFIRI or FOLFOX treatment in patients with poor prognosis of unresectable right-sided colorectal cancer.

Detailed description

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I (A-FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Arm II (A-FOLFOX/FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, fluorouracil IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. In both arms, treatment repeats every 2 weeks for up to 12 courses. After the 12 cycle treatment finished, investigator decides whether to keep the study drug. Treatment continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity. If treatment with oxaliplatin or irinotecan is difficult due to side effects, treatment with bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity. Patients undergo serum extraction and blood sample collection periodically for genomic, ctDNA and translational study. Patients also undergo collection of tumoral sections from paraffin embedded primary and/or metastatic lesions periodically for immunohistochemical analyses. After completion of study treatment, patients are followed every 6 months for survival and other treatments.

Conditions

• Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination Chemotherapy
• Unresectable Metastatic Right-sided Colon Cancer, Stage IV

Interventions

Type	Name	Description
DRUG	A-FOLFOXIRI	Arm I (A-FOLFOXIRI) Biological: bevacizumab Given IV Drug: fluorouracil Given IV Drug: irinotecan hydrochloride Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV
DRUG	Arm II (A-FOLFOX/A-FOLFIRI)	Arm II (A-FOLFOX/A-FOLFIRI) Biological: bevacizumab Given IV Drug: fluorouracil Given IV Drug: irinotecan hydrochloride Given IV Drug: leucovorin calcium Given IV

Timeline

• Start date: 2019-01-03
• Primary completion: 2024-06-01
• Completion: 2024-06-01
• First posted: 2018-08-22
• Last updated: 2020-10-19

Locations

1 site across 1 country: South Korea