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Sun Yat-sen UniversityPD-1 + FOLFOXIRI vs CAPOX as Total Neoadjuvant Therapy for pMMR Low Rectal Cancer Phase 3 382
Clinical Trial NCT07277842 is designed to study Treatment for Locally Advanced Low Rectal Adenocarcinoma, pMMR (Microsatellite Stable Rectal Cancer). This Phase 3 interventional study is not yet recruiting. Enrollment is planned to begin on 29 December 2025 until the study accrues 382 participants. Led by Sun Yat-sen University, this study is expected to complete by 29 December 2028. The latest data from ClinicalTrials.gov was last updated on 11 December 2025.
Brief Summary
The goal of this clinical trial is to find out if adding a PD-1 antibody (serplulimab) to FOLFOXIRI chemotherapy and radiotherapy works better than CAPOX chemotherapy with radiotherapy as total neoadjuvant therapy for adults with pMMR locally advanced low rectal cancer. It will also look at the safety of these treatments and how they affect long-term outcomes such as organ preservation and survival.
The main questio...
Show MoreOfficial Title
A Multicenter, Prospective, Phase III Randomized Controlled Trial of PD-1 Antibody Plus FOLFOXIRI Combined With Radiotherapy Versus CAPOX Combined With Radiotherapy as Total Neoadjuvant Therapy for pMMR Locally Advanced Low Rectal Cancer
Conditions
Locally Advanced Low Rectal AdenocarcinomapMMR (Microsatellite Stable Rectal Cancer)Other Study IDs
- 2025-FXY-302
NCT ID Number
Start Date (Actual)
2025-12-29
Last Update Posted
2025-12-11
Completion Date (Estimated)
2028-12-29
Enrollment (Estimated)
382
Study Type
Interventional
PHASE
Phase 3
Status
Not yet recruiting
Keywords
pMMR locally advanced rectal cancer
total neoadjuvant therapy
PD-1 antibody
serplulimab
watch-and-wait
total neoadjuvant therapy
PD-1 antibody
serplulimab
watch-and-wait
Primary Purpose
Treatment
Design Allocation
Randomized
Interventional Model
Parallel
Masking
None (Open Label)
Arms / Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalExperimental: Serplulimab + FOLFOXIRI + Radiotherapy Participants in this arm will receive a PD-1 antibody (serplulimab) in combination with FOLFOXIRI chemotherapy and long-course pelvic radiotherapy as total neoadjuvant therapy before surgery. Treatment will be given according to the study protocol, with regular safety monitoring and response assessments. | Serplulimab Serplulimab will be administered intravenously in combination with FOLFOXIRI chemotherapy and long-course pelvic radiotherapy as part of total neoadjuvant therapy in the experimental arm. FOLFOXIRI chemotherapy The FOLFOXIRI chemotherapy regimen (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) will be administered according to the study protocol as part of total neoadjuvant therapy in the experimental arm, in combination with serplulimab and long-course pelvic radiotherapy. Long-course pelvic radiotherapy Long-course pelvic external beam radiotherapy will be delivered according to institutional standards as part of total neoadjuvant therapy in both study arms, in combination with chemotherapy (FOLFOXIRI plus serplulimab in the experimental arm or CAPOX in the active comparator arm). |
Active ComparatorActive Comparator: CAPOX + Radiotherapy Participants in this arm will receive CAPOX chemotherapy and long-course pelvic radiotherapy as total neoadjuvant therapy before surgery. Treatment will be given according to the study protocol, with regular safety monitoring and response assessments. | CAPOX chemotherapy The CAPOX chemotherapy regimen (capecitabine plus oxaliplatin) will be administered according to the study protocol as part of total neoadjuvant therapy in the active comparator arm, in combination with long-course pelvic radiotherapy. Long-course pelvic radiotherapy Long-course pelvic external beam radiotherapy will be delivered according to institutional standards as part of total neoadjuvant therapy in both study arms, in combination with chemotherapy (FOLFOXIRI plus serplulimab in the experimental arm or CAPOX in the active comparator arm). |
Primary Outcome Measures
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
3-year Event-Free Survival (EFS) | Event-free survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: (1) locoregional failure, including unresectable primary tumor after completion of total neoadjuvant therapy, R2 resection (macroscopic residual tumor), or local bed recurrence after R0-R1 resection; (2) distant metastasis; (3) new invasive primary colorectal cancer; or (4) death from any cause. Patients without an event at the time of analysis will be censored at the date of the last tumor assessment. | Up to 3 years after randomization |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Clinical Complete Response (cCR) Rate | Proportion of participants achieving clinical complete response (cCR) after completion of total neoadjuvant therapy. cCR will be assessed by digital rectal examination, endoscopy, pelvic MRI and serum CEA according to predefined criteria (no palpable tumor, endoscopic whitening or telangiectasia only, fibrotic signal on MRI without residual tumor or nodes, and normal CEA). | At 10-14 weeks after completion of radiotherapy (response assessment prior to definitive management) |
Anal Sphincter Preservation Rate | Proportion of participants who achieve anal sphincter preservation, defined as undergoing sphincter-preserving surgery (e.g., low anterior resection, intersphincteric resection) or managed with a watch-and-wait strategy without permanent stoma at last follow-up. | From randomization to definitive management (surgery or decision for watch-and-wait) and last follow-up, up to approximately 1 year after randomization |
Incidence of Treatment-related Adverse Events During Total Neoadjuvant Therapy | Number and proportion of participants experiencing treatment-related adverse events during total neoadjuvant therapy, graded according to NCI-CTCAE version 5.0. Both overall adverse events and grade 3-5 toxicities related to chemotherapy, immunotherapy, or radiotherapy will be summarized. | From first dose of study treatment until 30-90 days after completion of chemotherapy/radiotherapy or surgery, up to approximately 1 year after randomization |
Participation Assistant
Eligibility Criteria
Eligible Ages
Adult, Older Adult
Minimum Age
18 Years
Eligible Sexes
All
- Histologically confirmed rectal adenocarcinoma.
- pMMR status documented by immunohistochemistry (MSH1, MSH2, MSH6 and PMS2 all positive) or by MSI testing showing MSS or MSI-L.
- Primary tumor located within 5 cm from the anal verge on pelvic MRI.
- Clinical stage cT3-4bN0M0 or cTxN+M0, with or without positive mesorectal fascia (MRF) and/or extramural vascular invasion (EMVI), and assessed by the multidisciplinary team as resectable with the potential for R0 resection.
- No clinical or radiologic evidence of bowel obstruction.
- No prior colorectal surgery.
- No prior chemotherapy or radiotherapy.
- No prior treatment with biologic agents (e.g., monoclonal antibodies), immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4), or other investigational drugs.
- Age 18 to 75 years (inclusive).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Estimated life expectancy > 2 years.
- Adequate bone marrow function: WBC > 3.5 × 10^9/L; platelets > 100 × 10^9/L; hemoglobin > 80 g/L.
- Adequate liver function: ALT and AST ≤ 1.5 × upper limit of normal (ULN); total bilirubin < 23.0 μmol/L.
- Adequate renal function: eGFR ≥ 60 mL/min/1.73 m² (CKD-EPI) or creatinine clearance (Ccr) ≥ 60 mL/min.
- Ability to understand and willingness to sign a written informed consent form.
- Evidence of inguinal or lateral pelvic lymph node metastasis (lymph node short-axis diameter ≥ 7 mm or MRI features typical for metastatic lymph nodes).
- Clinically significant cardiac disease, including arrhythmias requiring anti-arrhythmic treatment (except β-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), or congestive heart failure > NYHA class II.
- Uncontrolled severe hypertension.
- History of HIV infection or active chronic hepatitis B (HBV DNA > 2 × 10^3 IU/mL) or hepatitis C (HCV RNA > 1 × 10^3 IU/mL).
- Active pulmonary tuberculosis under treatment or having received anti-tuberculosis therapy within 1 year before screening.
- Other active severe infections (as defined by NCI-CTCAE v5.0).
- Evidence of distant metastasis outside the pelvis before treatment.
- Cachexia or decompensated organ dysfunction.
- Prior pelvic or abdominal radiotherapy.
- Multiple primary colorectal cancers.
- History of seizures requiring ongoing treatment (e.g., corticosteroids or anti-epileptic drugs).
- History of another malignancy within the past 5 years, except adequately treated cervical carcinoma in situ or basal cell carcinoma of the skin.
- Drug or alcohol abuse, or any medical, psychological, or social condition that, in the investigator's judgment, could interfere with study participation or the evaluation of study results.
- Any active autoimmune disease or history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, or hypothyroidism).
- Receipt of any prophylactic vaccine against infectious diseases (e.g., influenza, varicella) within 4 weeks before enrollment.
- Requirement for long-term immunosuppressive therapy or systemic/local corticosteroids at immunosuppressive doses (equivalent to > 10 mg/day of prednisone or other corticosteroids).
- Known or suspected allergy or hypersensitivity to any study drug or to any component of the study treatments.
- Any unstable condition or other circumstance that may, in the opinion of the investigator, compromise patient safety or study compliance.
- Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use adequate contraception during the study.
- Refusal or inability to provide written informed consent.
Sun Yat-sen University1239 active studies to exploreStudy Responsible Party
ZHI-ZHONG PAN, Principal Investigator, Professor, Sun Yat-sen University
Study Central Contact
Contact: Junzhong Lin, MD, +862087343124, [email protected]
1 Study Locations in 1 Countries
None Selected
Sun Yat-Sen University Cancer Center, Guangzhou, None Selected, 510060, China
Junzhong Lin, Contact, 02087343124, [email protected]