CtDNA in Adjuvant Chemotherapy of Stage III Colon Cancer (REVISE Trial)

NCT ID: NCT06242418

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-25

Study Completion Date

2026-12-31

Brief Summary

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Colon cancer is one of the most common malignant tumors with an increasing incidence rate in China. Surgical resection is still the main treatment for colon cancer at present. Radical surgery followed by three/six months chemotherapy is the standard of care for stage III colon cancer; however, patients with different risk factors have different prognosis. The IDEA trial divided stage III colon cancer patients into low-risk (T1-3/N1) and high-risk (T4 or N2) groups, and showed that for some low-risk patients, three months chemotherapy did not decrease survival outcomes, while for some high-risk patients, the recurrence risk was still high even after six months chemotherapy. Therefore, it's worth to explore other risk stratification factors beyond T and N stage for these patients.

Circulating tumor DNA (ctDNA) is derived from cancer cells and can be detected in blood. Literatures have reported that ctDNA can be used for tumor diagnosis, therapeutic monitoring, and prognosis assessment in multiple cancers, including colon cancer. The GERCOR-PRODIGE trial, an accompanying study of IDEA, reported that in the high-risk group of stage III colon cancer, patients with ctDNA-positive and receiving six months chemotherapy had similar prognosis to these with ctDNA-negative and receiving three months chemotherapy; in the low-risk group, patients with ctDNA-negative and receiving three or six months chemotherapy had similar prognosis to patients with ctDNA-positive and receiving 6 months chemotherapy, but patients with ctDNA-positive and receiving three months chemotherapy had the worst prognosis. The results of this trial suggests that ctDNA can be potentially used as a further stratification factor to guide adjuvant chemotherapy for stage III colon cancer.

Several RCTs have shown that double-drug regimens chemotherapy based on oxaliplatin (FOLFOX and XELOX) can improve the prognosis of patients with stage III colon cancer. Therefore, the ESMO, NCCN, and CSCO guidelines recommend FOLFOX or XELOX for stage III colon cancer. The 2-year disease-free survival rate of these patients who received FOLFOX or XELOX chemotherapy was about 80%. It is worth to further explore how to improve the prognosis of these patients. Recently, the triple-drug regimens of oxaliplatin, irinotecan, and fluoropyrimidine (FOLFOXIRI) has been found to be superior to FOLFOX or XELOX for metastatic colorectal cancer in terms of response rate and survival. Currently, research on FOLFOXIRI plus targeted therapy in metastatic colorectal cancer is progressing rapidly, but there is little research on the use of FOLFOXIRI as adjuvant chemotherapy for stage III colon cancer. There is an ongoing international multicenter phase III RCT comparing FOLFOXIRI and FOLFOX6 adjuvant chemotherapy for high-risk stage III colon cancer patients, but it did not further stratify patients based on postoperative ctDNA status, which may result in some patients receiving excessive chemotherapy.

The present study plans to enroll patients with stage III colon cancer with positive ctDNA within 1 month after surgery. These patients will receive 2 cycles of XELOX chemotherapy followed by retesting ctDNA. During the waiting period of the ctDNA results (approximately 3 weeks due to the testing time), all patients will receive another cycle of XELOX chemotherapy. If the ctDNA remains positive, the patients will be randomly assigned to receive 8 cycles of FOLFOXIRI as intensified adjuvant chemotherapy or 5 cycles of XELOX regimen as standard adjuvant chemotherapy. If the ctDNA is negative, the patients will continue to receive 5 cycles of XELOX chemotherapy. Within 3 weeks after the completion or termination of chemotherapy, ctDNA will be retested again. The aims of this study are to explore the value of ctDNA in surveillance of chemosensitivity and to preliminarily evaluate whether the intensified chemotherapy with FOLFOXIRI can increase ctDNA clearance as well as its safety in stage III colon cancer.

Detailed Description

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Conditions

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Colon Cancer

Keywords

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colon cancer ctDNA adjuvant chemotherapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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FOLFOXIRI

Eight cycles of FOLFOXIRI: Oxaliplatin 85mg/m2 ivgtt over 2 hours on day 1, Irinotecan 165mg/m2 ivgtt over 90 minutes on day 1, Calcium folinate 400mg/m2 ivgtt over 2 hours on day 1, 5-Fluorouracil 2400mg/m2 civ48h; Each cycle lasts for 2 weeks.

Group Type EXPERIMENTAL

FOLFOXIRI

Intervention Type DRUG

Eight cycles of FOLFOXIRI: Oxaliplatin 85mg/m2 ivgtt over 2 hours on day 1, Irinotecan 165mg/m2 ivgtt over 90 minutes on day 1, Calcium folinate 400mg/m2 ivgtt over 2 hours on day 1, 5-Fluorouracil 2400mg/m2 civ48h; Each cycle lasts for 2 weeks.

XELOX

Five cycles of XELOX: Oxaliplatin 130mg/m2 on day 1, Capecitabine 1000mg/m2 bid from day 1 to day 14; Each cycle lasts for 3 weeks.

Group Type ACTIVE_COMPARATOR

XELOX

Intervention Type DRUG

Five cycles of XELOX: Oxaliplatin 130mg/m2 on day 1, Capecitabine 1000mg/m2 bid from day 1 to day 14; Each cycle lasts for 3 weeks.

Interventions

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FOLFOXIRI

Eight cycles of FOLFOXIRI: Oxaliplatin 85mg/m2 ivgtt over 2 hours on day 1, Irinotecan 165mg/m2 ivgtt over 90 minutes on day 1, Calcium folinate 400mg/m2 ivgtt over 2 hours on day 1, 5-Fluorouracil 2400mg/m2 civ48h; Each cycle lasts for 2 weeks.

Intervention Type DRUG

XELOX

Five cycles of XELOX: Oxaliplatin 130mg/m2 on day 1, Capecitabine 1000mg/m2 bid from day 1 to day 14; Each cycle lasts for 3 weeks.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age 18-75 years, regardless of gender.
2. Tumor located in the colon (the distance from the lower margin of the tumor to the anus is greater than 12 cm).
3. Radical surgery performed, with pathological stage III (T1-4N1-2M0) (AJCC TNM staging, 8th edition, 2017).
4. No local or distant tumor recurrence was found in imaging examination.
5. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1.
6. adequate organ function: Hemoglobin ≥ 9 g/dL; WBC ≥ 3.5 × 109/ L; Neutrophils ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); ALT and AST ≤ 2.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 × ULN.
7. No history of allergy to fluoropyrimidines or platinum-based drugs.
8. Voluntarily participating in this study, signing an informed consent form, good compliance, and cooperation with follow-up.

Exclusion Criteria

1. History of other malignant tumors within the past five years (excluding basal cell carcinoma and/or cervical carcinoma in situ after radical surgery).
2. Patients with BRAF mutation status
3. Patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status
4. Previous chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc., for colon cancer.
5. Patients considering lynch syndrome.
6. Severe cardiovascular or cerebrovascular diseases, liver or kidney dysfunction, severe primary hematological diseases.
7. severe mental disorders
8. Any unstable condition or situation that may harm patient safety or compliance with the study, such as fertility needs, pregnancy, breastfeeding, depression, bipolar disorder, obsessive-compulsive disorder, or schizophrenia.
9. Recently participated in or currently participating in other clinical trials of drugs.
10. Patients deemed unsuitable for participation in this study by the investigator.

Withdrew Criteria

1. Severe adverse reactions to chemotherapy and being unable to continue chemotherapy
2. Metastatic or recurrence disease prior to randomization
3. Refusing further treatment at any time without reason
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GeneCast Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role collaborator

West China Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ziqiang Wang,MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Site Status RECRUITING

West China Hospital of Sichuan University

Chengde, Sichuan, China

Site Status RECRUITING

People's Hospital of Sichuan Province

Chengdu, Sichuan, China

Site Status RECRUITING

Shang Jin Hospital of West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, China

Site Status RECRUITING

The Third People's Hospital of Chengdu

Chengdu, Sichuan, China

Site Status RECRUITING

West China Tianfu Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

Site Status RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Ziqiang Wang

Role: CONTACT

Phone: +8685422480

Email: [email protected]

Qingbin Wu

Role: CONTACT

Phone: +8685422480

Email: [email protected]

Facility Contacts

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Zhen Yunhuan

Role: primary

Ziqiang Wang

Role: primary

Pang Minghui

Role: primary

Wei Mingtian

Role: primary

Liu Chao

Role: primary

Zhang Yuanchuan

Role: primary

Wang Meng

Role: backup

Deng Xiangbing

Role: primary

Zeng Yujian

Role: primary

Li Yunfeng

Role: primary

Liu Ping

Role: backup

References

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Zhou J, Huang J, Zhou Z, Fan R, Deng X, Qiu M, Wu Q, Wang Z. Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial). BMJ Open. 2025 Jan 2;15(1):e090394. doi: 10.1136/bmjopen-2024-090394.

Reference Type DERIVED
PMID: 39753246 (View on PubMed)

Other Identifiers

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2023#1998

Identifier Type: -

Identifier Source: org_study_id