161TiP - A phase II study of mFOLFOXIRI after metastasectomy in patients with oligometastatic colorectal cancer (FANTASTIC study)

Background

The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. Although the prognostic role of circulating-tumor DNA (ctDNA) was reported recently, it is yet to be determined which drug regimen is most effective for ctDNA-positive oligometastatic CRC. Thus, we initiated a phase II trial to evaluate the feasibility and efficacy of modified-FOLFOXIRI in CRC patients with oligometastases and to monitor patient’s response to therapy via ctDNA analysis.

Trial design

Oligometastatic CRC patients planning to undergo curative surgery were registered. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m², oxaliplatin 85 mg/m², l-leucovorin (l-LV) 200 mg/m², and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m² every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. Patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI, were allocated to the observation arm, in which standard care is provided. Blood is drawn before surgery, 28 days, 4 and 7 months after surgery for ctDNA analysis. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are survival outcomes in ctDNA negative and positive groups. ctDNA analysis will be performed retrospectively using a clinically validated, personalized 16-plex mPCR-NGS assay (Signatera^{TM, Natera, Inc.}). The sample size in the treatment arm was estimated to be 36 patients in order to achieve 70% power, with the hypothesis that the primary endpoint has an expected value of 50% and threshold value of 35% using one-sided testing at a significance level of 10%. Assuming half of the patients at the first registration would proceed to the observational arm, a total of 85 patients were expected to be enrolled from 11 institutions participating in Japan Clinical Oncology Group (JCOG). First patient-in was on July 2020. Accrual completed in February 2024, among whom 39 patients were allocated to mFOLFOXIRI arm.

Clinical trial identification

jRCTs051200026; First released on 8th June 2020.

Legal entity responsible for the study

The authors.

Funding

Japanese Society of Clinical Oncology.

Disclosure

M. Ikeda: Financial Interests, Personal, Invited Speaker: Taiho, Bayer, Pfizer; Financial Interests, Personal, Advisory Role: Daiichi Sankyo. K. Kataoka: Financial Interests, Personal, Invited Speaker: Merck Biopharma, Eli Lilly, Japan, Takeda; Financial Interests, Institutional, Research Grant: Japanese Society of Clinical Oncology. K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. K. Mori: Financial Interests, Personal, Speaker’s Bureau: Chugai, Ono, Daiichi Sankyo, Eli Lilly. N. Matsuhashi: Financial Interests, Personal, Invited Speaker: Abbott, Asahi Kasei Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, EA Pharma, Eisai, Eli Lilly, Gunze Medical, Kaken Pharm, Kyowa Kirn, MC Medical, Merck Biopharma, Miyasarin, MSD, Novartis, Ono, Taiho, Takeda, Terumo, Tsumura, Viatris, Yakult Honsha; Financial Interests, Personal, Research Grant: Taiho, Chugai, Nippon Kayaku. M. Shiozawa: Financial Interests, Personal, Invited Speaker: Lilly Japan, Merck Serono, Taiho Pharmaceutical, Yakult Honsha, Takeda, Ono Pharmaceutical, Johnson & Johnson, Kaken. M. Gotoh: Financial Interests, Personal, Invited Speaker, speaker: Ono Pharmaceutical Co., Ltd., MSD K.K.; Financial Interests, Institutional, Funding: Chugai Pharma, Taiho Pharmaceutical, Nippon Kayaku. S. Sharma, J. Ensor: Other, Personal, Full or part-time Employment: Natera Inc. A. Jurdi: Financial Interests, Institutional, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. M.C. Liu: Non-Financial Interests, Personal, Full or part-time Employment: Natera. Inc; Financial Interests, Personal, Stocks/Shares: Natera. Inc; Financial Interests, Personal, Research Grant: Eisai, Exact Sciences, Genentech, Tesaro; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Celgene, Roche, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. All other authors have declared no conflicts of interest.