113TiP - Prospective observational study monitoring circulating tumour DNA in resectable colorectal cancer patients undergoing radical surgery: GALAXY study in CIRCULATE-Japan

Background

Adjuvant chemotherapy has reduced the risk of recurrence and improved survival in patients with resected colorectal cancer (CRC). Early clinical utility of circulating tumor DNA (ctDNA) pre- and post-surgery has been reported across various solid tumor subtypes including CRC. Analysis of ctDNA status can be utilized as a predictor biomarker for stratifying patients based on their risk of recurrence and to monitor the effectiveness of adjuvant chemotherapy.

Trial design

GALAXY is a prospective observational study to monitor the ctDNA status and to establish the registry data in patients with stage II-IV CRC who will undergo a radical surgery. The study utilizes a personalized, tumor-informed ctDNA assay (Signatera™ bespoke multiplex-PCR NGS assay) that tracks patient-specific somatic single nucleotide variants present in plasma based on the whole-exome sequencing of tumor tissue. A total of 2500 patients will be enrolled at 146 sites and will be followed-up for 7 years. Blood samples will be collected at pre-surgery and post-surgery at 1, 3, 6, 9, 12, 18, and 24 months. Patients will also undergo regular radiologic assessment at pre-specified timepoints. Mutations in RAS, BRAF and microsatellite instability will be analyzed using PCR. The primary endpoint of the study is disease-free survival and secondary endpoints are overall survival, analysis of ctDNA status at each time point, and association between clinical characteristic and genetic alterations. Based on the ctDNA results in the GALAXY trial, patients can be enrolled either of the two distinct investigator-initiated phase III trials: the VEGA trial (treatment de-escalation) or the ALTAIR trial (treatment escalation). The VEGA trial assesses the non-inferiority of observation vs. adjuvant CAPOX in GALAXY participants who are high-risk stage II or low risk stage III CRC and show absence of ctDNA one-month post-surgery. The ALTAIR trial evaluates the superiority of FTD/TPI over placebo in GALAXY participants with ctDNA status that remains positive after the standard therapy. Moreover, additional tumor tissue and blood samples will also be banked for multi-omics analysis.

Clinical trial identification

UMIN000039205 on 01/20/2020.

Legal entity responsible for the study

CIRCULATE-Japan.

Funding

This study is funded by Japan Agency for Medical Research and Development (AMED).Grant number: JP19ck0106447.

Disclosure

D. Kotani: Honoraria (self): Takeda; Honoraria (self): Chugai; Honoraria (self): Lilly; Honoraria (self): Merck Biopharma; Honoraria (self): Taiho; Honoraria (self): Sysmex. E. Oki: Speaker Bureau/Expert testimony: Bayer Yakuhin; Speaker Bureau/Expert testimony: Chugai Pharmaceutical Co., Ltd; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co., Ltd.; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: Yakult Honsha Co., Ltd.; Speaker Bureau/Expert testimony: Merck Serono; Speaker Bureau/Expert testimony: Takeda Pharmaceutical Co., Ltd. H. Taniguchi: Honoraria (self): Takeda; Honoraria (self): Chugai; Honoraria (self): Taiho. Y. Nakamura: Research grant/Funding (self): Ono; Research grant/Funding (self): Taiho. T. Kato: Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Takeda Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Bayer Yakuhin Ltd.; Honoraria (self): Sanofi K.K.; Honoraria (self): Yakult Honsha Co. Ltd. T. Yamanaka: Honoraria (self), Research grant/Funding (self): Takeda Pharma; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Taiho Pharma; Honoraria (self), Research grant/Funding (self): Daiichi-Sankyo; Honoraria (self), Research grant/Funding (self): Ono Pharma; Research grant/Funding (self): Merck Biopharma; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (self): Bayer. A. Aleshin, P. Billings: Full/Part-time employment: Natera Inc. T. Yoshino: Research grant/Funding (self): Novartis Pharma K.K; Research grant/Funding (self): MSD. K.K.; Research grant/Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (self): Sanofi K.K.; Research grant/Funding (self): Daiichi Sankyo Company, Limited; Research grant/Funding (self): Parexel International Inc.; Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Research grant/Funding (self): GlaxoSmithKline K.K.. All other authors have declared no conflicts of interest.