508TiP - PRODIGE 68 - UCGI 38 - SOREGATT: A randomized phase II study comparing the sequences of regorafenib (reg) and trifluridine/tipiracil (t/t) after failure of standard therapies in patients (pts) with metastatic colorectal cancer (mCRC)

Background

First-line treatment for mCRC pts consists of a fluoropyrimidine-based chemotherapy (5-FU or capecitabine combined with oxaliplatin and/or irinotecan) with VEGF or EGFR inhibitors. Once these treatment options have been used, or are no longer appropriate, pts are eligible for either reg or t/t treatment. Although both treatments are approved in mCRC, no randomised trial has investigated the sequence of reg and t/t. The optimal strategy to extend survival while maintaining quality of life still needs to be determined. We have designed this trial to evaluate both treatment sequences and determine the best one in this setting.

Trial design

This international, randomized phase II, open-label trial is designed to compare the feasibility of the treatment sequences: reg followed by t/t vs t/t followed by reg. Pts ≥18 years, with mCRC, ECOG PS 0-1, after failure of fluoropyrimidine-based chemotherapy combined with oxaliplatin and/or irinotecan as well as EGFR (if RAS wild-type) and/or VEGF inhibitors are enrolled. Reg will be given according to ReDOS dose-escalation scheme at 1^st cycle (increasing from 80 mg to 160 mg daily over 3 weeks) to determine the highest dose tolerated that will be then used for the next cycles (3 weeks followed by 1 week off). T/t 35 mg/m² will be taken orally twice daily on D1-D5 and D8-D12 of each 4-week cycle. The primary endpoint is the treatment feasibility of the 2 sequences, assessed as the percentage of pts able to receive at least 2 cycles of both treatments, which corresponds to the first tumor evaluation at each line. If a pt does not receive the second treatment, he will be considered a failure. Secondary endpoints are overall survival, progression-free survival, disease control rate, objective response rate, time to treatment failure, time to ECOG PS ≥2 deterioration, quality of life and safety. We assume that 50% of the pts receiving t/t will be able to receive further treatment as compared to 65% with reg. With a Chi-square test between the 2 arms, a bilateral α-risk of 5% and a power of 80%, 170 pts are required in each arm. Since November 2020, 42 pts are enrolled in 14 sites.

Clinical trial identification

NCT04450836 - initial release 24 June 2020 EudraCT 2019-004196-39.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER, a private, non-profit French healthcare cooperative group, with its registered offices at 101, rue de Tolbiac, 75654 Paris, France.

Funding

Bayer HealthCare Pharmaceuticals Inc.

Disclosure

M.P. Ducreux: Financial Interests, Institutional, Writing Engagements, funding for medical writing: BeiGene; Financial Interests, Institutional, Sponsor/Funding, Contract for partial funding of a study: Roche; Financial Interests, Institutional, Sponsor/Funding, Contract for funding of a study: Bayer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Servier; Financial Interests, Institutional, Advisory Board: Merk Serono; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Ipsen. M. Ben Abdelghani: Financial Interests, Institutional, Advisory Board: Servier; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Expert Testimony: Roche; Financial Interests, Institutional, Expert Testimony: Ipsen; Financial Interests, Institutional, Expert Testimony: Amgen. D. Tougeron: Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Expert Testimony: Amgen; Financial Interests, Institutional, Expert Testimony: BMS; Financial Interests, Institutional, Expert Testimony: Merck; Financial Interests, Institutional, Expert Testimony: MSD; Financial Interests, Institutional, Expert Testimony: Pierre Fabre; Financial Interests, Institutional, Expert Testimony: Roche; Financial Interests, Institutional, Expert Testimony: Sanofi; Financial Interests, Institutional, Expert Testimony: Servier; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Ipsen. D. Botsen: Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Pierre Fabre; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Servier. O. Bouche: Financial Interests, Institutional, Sponsor/Funding: Merk; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Grunenthal; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Servier; Financial Interests, Institutional, Sponsor/Funding: Pierre Fabre. H. Alexandre: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: B3TSI; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Advisory Board: ICOMED; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Qualword; Financial Interests, Institutional, Advisory Board: Sophia Genetics; Financial Interests, Institutional, Sponsor/Funding: Merk Serono; Financial Interests, Institutional, Sponsor/Funding: Tesaro; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: BioRad. J. Bachet: Financial Interests, Institutional, Project Lead: AstraZeneca; Financial Interests, Institutional, Project Lead: Roche; Financial Interests, Institutional, Project Lead: Amgen; Financial Interests, Institutional, Project Lead: Bayer; Financial Interests, Institutional, Project Lead: Merk; Financial Interests, Institutional, Project Lead: Pierre Fabre; Financial Interests, Institutional, Project Lead: SANOFI; Financial Interests, Institutional, Project Lead: Servier. All other authors have declared no conflicts of interest.