Clinical Trial: A Randomized Phase III Study Comparing Pathology Artificial Intelligence (AI)- and Circulating Tumor DNA (ctDNA)-Guided Adjuvant Chemotherapy with Standard Adjuvant Therapy for Patients with Curatively Resected High-Risk Stage II and Stage III Colon Cancer (Japan)

Tokyo, Sept. 3 -- UMIN Clinical Trials Registry (UMIN-CTR) received information related to the study (UMIN000062786) titled 'A Randomized Phase III Study Comparing Pathology Artificial Intelligence (AI)- and Circulating Tumor DNA (ctDNA)-Guided Adjuvant Chemotherapy with Standard Adjuvant Therapy for Patients with Curatively Resected High-Risk Stage II and Stage III Colon Cancer' on Sept. 2.

Study Type: Interventional

Study Design: Basic Design - Parallel Randomization - Randomized Blinding - Open -no one is blinded Control - Active

Primary Sponsor: Institute - National Cancer Center Hospital East

Condition: Condition - Patients with Curatively Resected High-Risk Stage II and Stage III Colon Cancer Classification by malignancy - Malignancy Genomic information - YES

Objective: Narrative objectives1 - This study aims to evaluate, in a prospective randomized international project, whether a postoperative adjuvant chemotherapy strategy based on recurrence risk assessment using CAPAI (Combined Analysis of Pathologists and Artificial Intelligence) with DoMore-v1-CE-CRC and molecular residual disease (MRD) detection by circulating tumor DNA (ctDNA) is non-inferior to standard postoperative adjuvant chemotherapy in terms of disease-free survival (DFS) among patients with high-risk stage II and stage III colon cancer who have undergone curative resection (experimental treatment group: Arm A vs. control group: Arm B).

The project will validate this hypothesis through an integrated analysis of data from randomized phase III trials conducted in Japan, the United Kingdom, and Norway. Data collected in Japan will be transferred to the Institute for Cancer Genetics and Informatics (ICGI) at Oslo University, where the pooled analyses will be performed jointly by ICGI and the University of Oxford.

If non-inferiority of the adjuvant chemotherapy strategy guided by CAPAI and MRD-based recurrence risk assessment is demonstrated, it may be possible to reduce the use of adjuvant chemotherapy while maintaining its efficacy in preventing cancer recurrence. Consequently, the number of patients requiring postoperative adjuvant chemotherapy could be decreased, potentially reducing the risk of treatment-related adverse effects and improving patient quality of life. Basic objectives2 - Safety,Efficacy

Intervention: Interventions/Control_1 - Arm A (Biomarker-Guided Arm) In Arm A, postoperative recurrence risk is assessed using both CAPAI (Combined Analysis of Pathologists and Artificial Intelligence) and circulating tumor DNA (ctDNA) testing. Patients classified as high-risk or intermediate-risk by CAPAI, or those with a positive ctDNA result, are considered to be at high risk of recurrence and will receive adjuvant chemotherapy at the discretion of the treating physician. In contrast, patients classified as low-risk by CAPAI and negative for ctDNA are considered to be at low risk of recurrence and will undergo observation without adjuvant chemotherapy. All patients will be followed for five years and will undergo ctDNA surveillance. ctDNA surveillance will be performed every three months during the first year and every six months during the second year. Interventions/Control_2 - Arm B (Standard Treatment Arm) In Arm B, CAPAI and ctDNA testing will be performed; however, the results will not be disclosed to the treating physician. Therefore, decisions regarding the indication for adjuvant chemotherapy and the treatment regimen will be made by the treating physician according to standard clinical practice, based on conventional clinical and pathological factors such as disease stage and pathological findings. Adjuvant chemotherapy, when indicated, will be initiated within six weeks after surgery. As in Arm A, all patients will be followed for five years and will undergo ctDNA surveillance.

Eligibility: Age-lower limit - 18 years-old <= Age-upper limit - Not applicable Gender - Male and Female Key inclusion criteria - Patients who meet all of the following inclusion criteria and none of the exclusion criteria will be eligible for enrollment in this study. (1) Histologically confirmed colonic adenocarcinoma, including tumors arising in the rectosigmoid colon as defined by the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, 9th Edition. (2) Aged 18 years or older at the time of informed consent. (3) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1. (4) Have undergone curative (R0) resection with D2 or D3 lymph node dissection. (5) Have high-risk Stage II disease (defined by the presence of at least one of the recurrence risk factors (a)-(e) below) or Stage III disease: (a) T4 disease (SE/SI/AI) (b) Fewer than 12 lymph nodes examined (c) Clinically diagnosed bowel obstruction, perforation, or penetration (d) Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous adenocarcinoma (e) Vascular, lymphatic, or perineural invasion (6) No radiological evidence of metastatic disease within 90 days prior to registration. (7) Availability of a surgically resected primary colon tumor specimen. (8) Adequate organ function within 35 days prior to registration. (9) Registration conducted 2 to 6 weeks after curative resection. (10) Enrollment in the MONSTAR-3.5 MUGEN Study. (11) Provision of written informed consent by the patient for participation in this study. Key exclusion criteria - (1) Two or more synchronous primary colon cancers. (2) History of prior malignancy. Eligible if recurrence-free for more than 5 years or if the malignancy was cured by local treatment, e.g. basal or squamous cell skin cancer, superficial bladder cancer, cervical cancer, carcinoma in situ, intramucosal carcinoma, or non-metastatic prostate cancer not requiring systemic therapy. (3) Known MSI-H or MMR deficiency. (4) Chemotherapy, immunotherapy, or radiotherapy within 6 months before registration. (5) Pregnant or breastfeeding women. (6) Unwillingness to use contraception during treatment and for 30 days thereafter. (7) History of bone marrow or solid organ transplantation. (8) Uncontrolled heart failure, angina, hypertension, arrhythmia, or diabetes. (9) Uncontrolled active seizure disorder. (10) Active or chronic infection requiring systemic therapy. (11) Grade 2 or higher sensory or motor neuropathy (CTCAE v5.0). (12) Positive HBsAg or HCV antibody. (13) Positive HIV antibody (Patients may be enrolled even if HIV antibody testing has not been performed). (14) Known DPD deficiency. (15) History of hypersensitivity to oxaliplatin, LV, 5-FU, or capecitabine. (16) Any condition deemed unsuitable by the Principal Investigator. Target Size - 1053

Recruitment Status: Recruitment status - Preinitiation Date of protocol fixation - 2026 Year 08 Month 26 Day Date of IRB - 2026 Year 09 Month 01 Day Anticipated trial start date - 2026 Year 09 Month 15 Day Last follow-up date - 2034 Year 03 Month 31 Day

To know more, visit https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071397

Disclaimer: Curated by HT Syndication.