KEY TAKEAWAYS
- The phase II trial aimed to assess the feasibility and efficacy of mFOLFOXIRI in pts CRC.
- The primary endpoint of the study is treatment compliance after 8 courses of mFOLFOXIRI.
The study addresses the uncertain survival benefits of adjuvant chemotherapy following surgical resection of oligometastases in colorectal cancer (CRC). Although, the prognostic role of circulating-tumor DNA (ctDNA) has been recently highlighted, yet the most effective drug regimen for ctDNA-positive oligometastatic CRC is still unknown.
Consequently, a phase II trial was initiated to assess the feasibility and efficacy of modified-FOLFOXIRI (mFOLFOXIRI) in pts with CRC with oligometastases and to monitor their response to therapy through ctDNA analysis.
Masataka Ikeda and the team aimed to evaluate the feasibility and efficacy of mFOLFOXIRI in pts with oligometastatic CRC.
Researchers designed this study to investigate the prognostic role of ctDNA, initiated a phase II trial to evaluate the feasibility and efficacy of mFOLFOXIRI in pts with oligometastatic CRC, while monitoring patient response to therapy through ctDNA analysis.
The study included pts with oligometastatic CRC who were planning to undergo curative surgery. After metastasectomy, these pts were enrolled in the treatment arm to receive 8 courses of mFOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin (l-LV) 200 mg/m2, and 46-hour continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m2 every 2 weeks), followed by 4 courses of 5-FU/l-LV.
Patients who did not meet eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI were placed in the observation arm, receiving standard care. Blood samples were drawn before surgery and at 28 days, 4 months, and 7 months post-surgery for ctDNA analysis.
The primary endpoint of the study is treatment compliance after 8 courses of mFOLFOXIRI, with key secondary endpoints being survival outcomes in ctDNA-negative and ctDNA-positive groups. ctDNA analysis will be performed retrospectively using a clinically validated, personalized 16-plex mPCR-NGS assay (SignateraTM, Natera, Inc.).
The treatment arm’s cohort size was approximately 36 pts to achieve 70% power, based on the hypothesis that the primary endpoint has an expected value of 50% and a threshold value of 35%, using 1-sided testing at a significance level of 10%. With an expectation that half of the patients at the first registration would proceed to the observational arm, a total of 85 pts were expected to be registered from 11 institutions in the Japan Clinical Oncology Group (JCOG). The first patient was registered in July 2020, and accrual was completed in February 2024, with 39 patients allocated to the mFOLFOXIRI arm.
The study is funded by Japanese Society of Clinical Oncology.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trial: https://jrct.niph.go.jp/latest-detail/jRCTs051200026
Ikeda M, Kataoka K, Yamada T, et al. (2024). “A phase II study of mFOLFOXIRI after metastasectomy in patients with oligometastatic colorectal cancer (FANTASTIC study).” Presented at ESMO-GI 2024, (Abstract 161TiP)
