Neoadjuvant CAPEOX Versus Upfront Surgery for Locally Advanced Colon Cancer With Elevated CEA: A Single-Center, Open-Label, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 主要终点
- 2-year Disease-Free Survival (2y-DFS)
研究概览
简要总结
The goal of this interventional clinical trial is to compare the efficacy of neoadjuvant chemotherapy versus upfront surgery in adults aged 18-70 years with stage II (high-risk)-III, non-MSI-H colon adenocarcinoma and elevated baseline CEA (>5 ng/mL) undergoing curative-intent treatment. This single-center, open-label, randomized controlled study will evaluate 2-year disease-free survival (2y-DFS) as the primary endpoint, with all study-related procedures-including longitudinal ctDNA-based molecular residual disease (MRD) monitoring, Immunoscore assessment, tumor tissue sequencing, and surveillance imaging-provided at no cost to participants. The main questions it aims to answer are:
- Does a treatment strategy involving neoadjuvant CAPOX followed by surgery improve 2y-DFS compared with upfront surgery followed by standard adjuvant chemotherapy?
- Do postoperative ctDNA-MRD status and its longitudinal dynamics predict 2y-DFS?
- Does combining ctDNA-MRD with Immunoscore enhance prognostic risk stratification for recurrence beyond either biomarker alone?
Participants will:
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Be randomized 1:1 (N=100) to one of two treatment pathways:
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Arm A: Neoadjuvant CAPOX × 4 cycles → curative surgery (R0 planned) → postoperative management per standard practice
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Arm B: Upfront curative surgery → postoperative standard adjuvant chemotherapy per guideline → routine surveillance
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Undergo baseline assessments prior to treatment initiation, including blood draw, colonoscopy, primary tumor next-generation sequencing (for personalized ctDNA-MRD assay development), and Immunoscore testing-all provided free of charge as part of the study.
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Provide postoperative blood samples for ctDNA-MRD testing at approximately postoperative day ~7 and day ~30 (before adjuvant therapy start, if applicable).
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During follow-up, provide serial blood samples every 3 months, aligned with routine surveillance visits, for repeat ctDNA-MRD analysis.
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Receive standard-of-care postoperative surveillance (including imaging and clinical evaluations) through 2 years, with all study-mandated assessments covered by the trial.
This trial integrates clinical intervention with comprehensive biomarker profiling to determine whether early systemic therapy alters MRD dynamics and improves outcomes in high-risk, CEA-elevated colon cancer.
详细描述
Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a leading cause of cancer-related mortality. In China, CRC incidence ranks among the top cancers, and CRC-related death constitutes a major public health burden. Approximately 80% of CRC patients present with non-metastatic disease (stages I-III), representing the primary population for whom recurrence prevention is critical. Despite guideline-recommended curative-intent surgery and perioperative systemic therapy, at least 30% of patients with resectable stage II-III colon cancer experience recurrence or distant metastasis after initial treatment. This underscores an urgent need for more effective therapeutic strategies and better tools for risk-adapted management.
Current adjuvant chemotherapy decisions for stage II (high-risk) and stage III colon cancer rely largely on TNM staging and clinicopathologic risk factors, which do not directly measure residual tumor burden. Consequently, some patients may be overtreated with unnecessary toxicity, while others at high risk of relapse may receive insufficient therapy. Elevated baseline carcinoembryonic antigen (CEA >5 ng/mL) is a well-established adverse prognostic factor in colon cancer and identifies a subgroup with higher recurrence risk. Emerging data also suggest that patients with proficient mismatch repair (pMMR)/non-MSI-H tumors-particularly those with elevated CEA-may benefit from early systemic intervention before surgery. Therefore, evaluating whether neoadjuvant chemotherapy improves outcomes compared with standard upfront surgery represents a clinically meaningful question in this high-risk population.
This trial is designed as a single-center, open-label, randomized controlled study to directly compare two perioperative treatment strategies in adults aged 18-70 years with stage II (high-risk)-III, non-MSI-H colon adenocarcinoma and baseline CEA >5 ng/mL. All participants will be randomly assigned (1:1) to either:
Arm A (Neoadjuvant CAPOX Pathway): 4 cycles of neoadjuvant CAPOX chemotherapy followed by curative-intent surgery (R0 planned), with postoperative management per standard guidelines; or Arm B (Upfront Surgery Pathway): immediate curative-intent surgery followed by standard adjuvant chemotherapy and routine surveillance.
The primary objective of the study is to determine whether the neoadjuvant approach improves 2-year disease-free survival (2y-DFS) compared with upfront surgery. Importantly, all study-mandated procedures-including tumor tissue sequencing, Immunoscore assessment, personalized ctDNA-MRD assay development, and serial blood-based MRD monitoring-are provided at no cost to participants as part of the research protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Age 18 to 70 years (inclusive) at the time of written informed consent. ECOG performance status 0-1, without deterioration within 2 weeks prior to enrollment; anticipated life expectancy ≥12 weeks.
- •Histologically or cytologically confirmed colon adenocarcinoma, non-MSI-H/dMMR, with pathologic stage (AJCC/UICC TNM 8th edition) of:
- •High-risk stage II, or Stage III. High-risk stage II features include: T4, poor/undifferentiated histology (high grade; excluding MSI-H), lymphovascular invasion, perineural invasion, preoperative bowel obstruction or tumor perforation, positive/unknown margin status, insufficient margin clearance, <12 lymph nodes examined, or high-grade tumor budding.
- •Tumor location consistent with colon cancer: distal tumor margin ≥12 cm from the anal verge on preoperative endoscopy.
- •Baseline serum CEA >5 ng/mL prior to treatment. No evidence of distant metastasis (distant organ and/or distant lymph node metastasis) based on comprehensive clinical evaluation.
- •Ability to provide required clinical data for study collection. Ability to provide adequate fresh tumor tissue from endoscopy and/or surgery for WES/NGS to develop an individualized ctDNA MRD panel, and ability to provide required blood samples for ctDNA testing (baseline, postoperative ~day 7, postoperative ~day 30).
- •Candidate for curative-intent R0 resection. Willing and able to comply with the protocol schedule, including regular follow-up visits and necessary treatments, and provides written informed consent.
排除标准
- •Participants will be excluded if any of the following apply:
- •Prior or concurrent other malignant tumor. Any severe comorbidity that, in the investigator's judgment, may significantly affect follow-up or short-term survival.
- •Any other medical condition, or social/psychological circumstance, that in the investigator's judgment makes the participant unsuitable for the study.
- •MSI-H/dMMR tumor. Evidence of metastatic disease by pathology, clinical assessment, or imaging, including isolated distant lesions, distant disease, or non-contiguous intraperitoneal metastasis.
- •Multiple primary colon cancers. Underwent open surgery at a non-colon site within 14 days prior to enrollment. Unable to provide required tumor tissue for WES/NGS or personalized MRD panel development, personalized MRD panel customization failure, or unable to provide required blood samples (baseline, postoperative ~day 7, postoperative ~day 30).
- •History of blood transfusion within 2 weeks prior to surgery or intraoperatively.
- •Unable to undergo contrast-enhanced CT or MRI for routine clinical follow-up. Fever ≥38°C within the past 7 days, or clinically significant active infection (including active tuberculosis), or active fungal/bacterial/viral infection requiring systemic therapy.
- •Inadequate bone marrow reserve or organ function meeting any of the following laboratory abnormalities (within 1 week prior to testing without corrective treatment):
- •ANC < 1.5 × 10⁹/L Platelets < 90 × 10⁹/L Hemoglobin < 90 g/L (<9 g/dL) ALT > 3 × ULN AST > 3 × ULN or total bilirubin > 1.5 × ULN Creatinine > 1.5 × ULN or creatinine clearance < 45 mL/min (Cockcroft-Gault) Albumin < 28 g/L Pregnant or breastfeeding, or planning pregnancy during the study period. Any other condition that, in the investigator's judgment, indicates the participant should not participate.
研究组 & 干预措施
Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy
Participants in this arm receive 4 cycles of standard neoadjuvant CAPOX (CAPEOX) prior to curative-intent surgery. Postoperative adjuvant chemotherapy is determined based on the postoperative pathologic stage and risk stratification (per current CSCO guideline criteria). High-risk stage III participants receive an additional 4 cycles of CAPOX. For low-risk stage III or stage II participants, either no additional adjuvant chemotherapy or an additional 4 cycles of capecitabine is administered, determined by the treating physician in discussion with the participant.
干预措施: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment (Diagnostic Test)
Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy
Participants in this arm receive 4 cycles of standard neoadjuvant CAPOX (CAPEOX) prior to curative-intent surgery. Postoperative adjuvant chemotherapy is determined based on the postoperative pathologic stage and risk stratification (per current CSCO guideline criteria). High-risk stage III participants receive an additional 4 cycles of CAPOX. For low-risk stage III or stage II participants, either no additional adjuvant chemotherapy or an additional 4 cycles of capecitabine is administered, determined by the treating physician in discussion with the participant.
干预措施: Neoadjuvant Chemotherapy (Drug)
Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy
Participants in this arm receive 4 cycles of standard neoadjuvant CAPOX (CAPEOX) prior to curative-intent surgery. Postoperative adjuvant chemotherapy is determined based on the postoperative pathologic stage and risk stratification (per current CSCO guideline criteria). High-risk stage III participants receive an additional 4 cycles of CAPOX. For low-risk stage III or stage II participants, either no additional adjuvant chemotherapy or an additional 4 cycles of capecitabine is administered, determined by the treating physician in discussion with the participant.
干预措施: Adjuvant chemotherapy (Drug)
Upfront R0-planned Surgery followed by adjuvant chemotherapy
In this arm, participants undergo upfront curative-intent (radical) surgery after standard preoperative assessment and staging. Postoperative adjuvant chemotherapy is administered per current CSCO guidelines based on pathologic stage and risk factors, with regimen selection determined by the treating physician in discussion with the patient.
干预措施: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment (Diagnostic Test)
Upfront R0-planned Surgery followed by adjuvant chemotherapy
In this arm, participants undergo upfront curative-intent (radical) surgery after standard preoperative assessment and staging. Postoperative adjuvant chemotherapy is administered per current CSCO guidelines based on pathologic stage and risk factors, with regimen selection determined by the treating physician in discussion with the patient.
干预措施: Adjuvant chemotherapy (Drug)
结局指标
主要结局
2-year Disease-Free Survival (2y-DFS)
时间窗: From date of surgery up to 24 months postoperatively.
Disease-free survival is defined as the time from curative-intent surgery to the first occurrence of any of the following events: (1) local recurrence, (2) distant metastasis, (3) a second primary colorectal cancer, or (4) death from any cause, whichever occurs first. Participants without an event will be censored at the last disease assessment.
次要结局
- 2-year Overall Survival (2y-OS)(From date of surgery up to 24 months postoperatively.)
- Local Recurrence Rate at 2 years(Up to 24 months postoperatively.)
研究者
Gong Chen
Vice Director of Colorectal Surgery, Cheif Surgeon
Sun Yat-sen University