Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer
G. Sommerhäuser,
A. Kurreck,
S. Stintzing,
V. Heinemann,
L. Fischer von Weikersthal,
T. Dechow,
F. Kaiser,
M. Karthaus,
I. Schwaner,
M. Fuchs,
A. König,
C. Roderburg,
I. Hoyer,
M. Quante,
A. Kiani,
S. Fruehauf,
L. Müller,
A. Reinacher-Schick,
T. J. Ettrich,
A. Stahler,
D. P. Modest
Affiliations
G. Sommerhäuser
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
A. Kurreck
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
S. Stintzing
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
V. Heinemann
German Cancer Consortium (DKTK), DKFZ
L. Fischer von Weikersthal
Gesundheitszentrum St. Marien
T. Dechow
Oncological Practice
F. Kaiser
Oncological Practice
M. Karthaus
Department of Hematology and Oncology, Klinikum Neuperlach/ Klinikum Harlaching
I. Schwaner
Oncological Practice Kurfuerstendamm
M. Fuchs
Department of Gastroenterology, Hepatology, and Gastrointestinal Oncology, München Klinik Bogenhausen
A. König
Department of Gastroenterology and Gastrointestinal Oncology Goettingen, University Medical Center Goettingen
C. Roderburg
Department of Gastroenterology, Hepatology, and Infectiology, University Medical Center Duesseldorf
I. Hoyer
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
M. Quante
Department of Gastroenterology, Hepatology, Endocrinology, and Infectiology, Albert-Ludwigs-Universität Freiburg
A. Kiani
Department of Medicine IV, Klinikum Bayreuth GmbH
S. Fruehauf
Department of Hematology, Oncology, and Palliative Care, Klinik Dr. Hancken GmbH
L. Müller
Onkologie UnterEms
A. Reinacher-Schick
Department of Hematology, Oncology and Palliative Care, Ruhr-University Bochum
T. J. Ettrich
Department of Internal Medicine, University Hospital Ulm
A. Stahler
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
D. P. Modest
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Abstract Background Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. Methods FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1–5 and 8–12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. Discussion To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy. Trial registration EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021.
