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. 2021 Jul;112(7):2915-2920.
doi: 10.1111/cas.14926. Epub 2021 Jun 7.

CIRCULATE-Japan: Circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer

Hiroya Taniguchi  1   2 , Yoshiaki Nakamura  1   3 , Daisuke Kotani  1 , Hiroki Yukami  1 , Saori Mishima  1 , Kentaro Sawada  1 , Hiromichi Shirasu  4 , Hiromichi Ebi  5 , Takeharu Yamanaka  6 , Alexey Aleshin  7 , Paul R Billings  7 , Matthew Rabinowitz  7 , Eiji Oki  8 , Ichiro Takemasa  9 , Takeshi Kato  10 , Masaki Mori  8   11 , Takayuki Yoshino  1
Affiliations

CIRCULATE-Japan: Circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer

Hiroya Taniguchi et al. Cancer Sci. 2021 Jul.

Abstract

Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE-Japan including three clinical trials. The GALAXY study is a prospectively conducted large-scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high-risk stage II or low-risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double-blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor-positive status in the GALAXY study. Therefore, CIRCULATE-Japan encompasses both "de-escalation" and "escalation" trials for ctDNA-negative and -positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA-guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.

Keywords: adaptive clinical trial design; adjuvant chemotherapy; circulating tumor DNA; colorectal cancer; trifluridine.

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Conflict of interest statement

Alexey Aleshin, Paul R Billings, Matthew Rabinowitz are from Natera Inc, San Carlos, CA, USA. Hiroya Taniguchi received lecture fees from Taiho and Chugai. Yoshiaki Nakamura received research funds from Taiho and Chugai. Eiji Oki received lecture fees from Taiho and Chugai. Daisuke Kotani received lecture fees from Taiho and Chugai. Takeshi Kato received lecture fees from Taiho and​ Chugai. Masaki Mori received research funds from Taiho and Chugai, and received lecture fee from Taiho and Chugai. Takayuki Yoshino received lecture fees from Taiho and Chugai, and research funds from Taiho and Chugai.

Figures

FIGURE 1
FIGURE 1
CIRCULATE‐Japan overview. ctDNA, circulating tumor DNA; F/U, follow up; FTD/TPI, trifluridine/tipiracil; mo, month; NAC, neoadjuvant chemotherapy; Op, operative; WES, whole‐exome sequencing
See this image and copyright information in PMC

References

    1. Nakamura Y, Taniguchi H, Ikeda M, et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM‐Japan GI‐SCREEN and GOZILA studies. Nat Med. 2020;26:1859‐1864. - PubMed
    1. Coombes RC, Page K, Salari R, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. 2019;25:4255‐4263. - PubMed
    1. Reinert T, Henriksen TV, Christensen E, et al. Analysis of plasma cell‐free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5:1124‐1131. - PMC - PubMed
    1. Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378:1177‐1188. - PMC - PubMed
    1. Yoshino T, Yamanaka T, Oki E, et al. Efficacy and long‐term peripheral sensory neuropathy of 3 vs 6 months of oxaliplatin‐based adjuvant chemotherapy for colon cancer: the ACHIEVE phase 3 randomized clinical trial. JAMA Oncol. 2019;5:1574‐1581. - PMC - PubMed

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