Randomized Study of Plasma ctDNA Methylation to Guide Adjuvant Chemotherapy Decisions in High-Risk T3N0 Colorectal Cancer
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Fudan University
- Enrollment
- 340
- Locations
- 1
- Primary Endpoint
- Patient's 2-year Progression-Free Survival
Overview
Brief Summary
This study will utilize ctDNA methylation detection to evaluate patients with high-risk T3N0 stage II colorectal cancer who are ctDNA-positive one month after surgery. It aims to investigate the impact of different adjuvant chemotherapy regimens on ctDNA clearance rates and their prognostic significance. By using postoperative ctDNA status to identify patients at high risk of recurrence, the study seeks to implement intensified chemotherapy strategies (treatment escalation) at an early stage, thereby improving ctDNA clearance and ultimately enhancing patient outcomes
Detailed Description
This study will utilize ctDNA methylation detection to evaluate patients with high-risk T3N0 stage II colorectal cancer who are ctDNA-positive one month after surgery. It aims to investigate the impact of different adjuvant chemotherapy regimens on ctDNA clearance rates and their prognostic significance. By using postoperative ctDNA status to identify patients at high risk of recurrence, the study seeks to implement intensified chemotherapy strategies (treatment escalation) at an early stage, thereby improving ctDNA clearance and ultimately enhancing patient outcomes
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years, regardless of sex;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of \>3 months;
- •Histologically confirmed postoperative pTNM stage high-risk stage II colorectal cancer;
- •Positive ctDNA status at 1 month after surgery;
- •Expected survival of \>12 months;
- •Ability to understand and willingness to sign a written informed consent form (personally or via a legally authorized representative/guardian), indicating that the subject understands the study objectives and required procedures and agrees to participate.
Exclusion Criteria
- •Receipt of neoadjuvant therapy prior to surgery;
- •Blood transfusion during surgery or within 2 weeks prior to surgery;
- •Pregnant or breastfeeding women, or individuals of reproductive potential who are not using adequate contraception;
- •History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer;
- •Uncontrolled primary brain tumors or central nervous system metastases, or presence of significant intracranial hypertension or neuropsychiatric symptoms;
- •Presence of severe or uncontrolled comorbidities, including but not limited to:Severe cardiac disease that remains unstable despite treatment, including myocardial infarction, congestive heart failure, unstable angina, symptomatic pericardial effusion, or unstable arrhythmia within 6 months prior to enrollment; Clearly diagnosed neurological or psychiatric disorders, including dementia or seizure disorders;Severe or uncontrolled infections;Active disseminated intravascular coagulation (DIC) or significant bleeding tendency;Significant impairment of major organ function;
- •Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation in this study.
Arms & Interventions
Single-agent chemotherapy group
The control group will receive postoperative capecitabine monotherapy for 6 months.
Intervention: Capecitabine (Drug)
doublet chemotherapy group
The intervention group will receive FOLFOX or CAPOX for 3 months. After 3 months of treatment, ctDNA status will be reassessed. Patients who convert to ctDNA-negative will receive capecitabine monotherapy for an additional 3 months, whereas those who remain ctDNA-positive will switch to FOLFIRI or CAPIRI for a further 3 months.
Intervention: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) (Drug)
Outcomes
Primary Outcomes
Patient's 2-year Progression-Free Survival
Time Frame: 2-year Progression-Free Survival
Two-year Progression-Free Survival (PFS) is defined as the proportion of patients who remain alive without evidence of disease progression or recurrence within 24 months from the date of surgery (or randomization, as specified in the protocol). Disease progression is determined according to radiologic, clinical, or pathological criteria.
Secondary Outcomes
- ctDNA-clearance Rate(3 months after initiation of adjuvant therapy.)
Investigators
Guoxiang Cai
Fudan University Shanghai Cancer Center
Fudan University