Short-course radiotherapy plus CAPOX chemotherapy with serplulimab and bevacizumab for mid-low MSS rectal cancer
A Single-Center, Prospective, Phase II Clinical Study to Evaluate the Preliminary Efficacy and Safety of Short-Course Radiotherapy Followed by CAPOX Chemotherapy Combined With Serplulimab and Bevacizumab as Total Neoadjuvant Therapy for MSS-Type, Mid-Low Locally Advanced Rectal Cancer
This trial will try short-course radiotherapy followed by CAPOX chemotherapy together with serplulimab and bevacizumab before surgery in people with mid-low MSS locally advanced rectal cancer to see if it is safe and shrinks tumors.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | First Affiliated Hospital of Wenzhou Medical University Academic / other |
| Drugs / interventions | immunotherapy, serplulimab, bevacizumab, chemotherapy |
| Locations | 1 site (Wenzhou, Zhejiang) |
| Trial ID | NCT07347951 on ClinicalTrials.gov |
What this trial studies
This is a single-center, phase II prospective trial of total neoadjuvant therapy for mid-low locally advanced MSS/pMMR rectal adenocarcinoma. Participants receive short-course radiotherapy followed by sequential CAPOX chemotherapy combined with the PD-1 antibody serplulimab and the anti-VEGF agent bevacizumab prior to planned surgery. The study aims to enroll about 30 patients between September 2025 and September 2027 and will collect safety and preliminary efficacy outcomes, including tumor response and surgical outcomes. Eligibility requires cT3-4 and/or node-positive disease confined to the mesorectum, tumor ≤10 cm from the anal verge, ECOG 0–1, and no prior anti-cancer or pelvic radiotherapy.
Who should consider this trial
Good fit: Adults 18–75 with mid-low locally advanced (cT3-4 and/or node-positive) MSS/pMMR rectal adenocarcinoma located ≤10 cm from the anal verge, ECOG 0–1, adequate labs, and no prior systemic or pelvic radiotherapy are the intended candidates.
Not a fit: Patients with MSI-H tumors, distant metastases, significant comorbidities, poor blood counts, prior anti-cancer or pelvic radiotherapy, or who cannot commit to serial visits and surgery are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could increase tumor downstaging and the chance of sphincter-preserving surgery while improving local control.
How similar studies have performed: Combining radiotherapy and chemotherapy with PD-1 blockade and anti-angiogenic therapy for MSS rectal cancer is experimental with some encouraging early-phase or translational signals but no definitive large-scale success to date.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* Patients who have a desire to preserve the anus and are willing to receive the entire course of neoadjuvant therapy.
* Aged between 18 and 75 years, with no gender restrictions.
* Diagnosed via pelvic MRI and rectoscopy with a tumor located ≤10 cm from the anal verge, with a clinical stage of cT3-4N0/+M0, and lymph nodes confined within the mesorectum.
* Histologically diagnosed with rectal adenocarcinoma; genetic testing indicates MSS or MSI-L, or immunohistochemistry of tumor biopsy indicates pMMR (positive for MSH1, MSH2, MSH6, and PMS2 proteins).
* ECOG performance status score of 0-1.
⑥ No prior antitumor therapy, immunotherapy, anti-angiogenic therapy, or pelvic radiotherapy before inclusion.
⑦ Laboratory tests must meet the following criteria: i. White blood cell count ≥3.5×10⁹/L, absolute neutrophil count ≥1.8×10⁹/L, platelet count ≥100×10⁹/L, and hemoglobin ≥100 g/L; ii. INR ≤1.5, and APTT ≤1.5 times the upper limit of normal, or partial thromboplastin time (PTT) ≤1.5 times the upper limit of normal; iii. Total bilirubin ≤1.25 times the upper limit of normal; ALT and AST ≤3 times the upper limit of normal; serum albumin ≥28 g/L; iv. 24-hour creatinine clearance rate ≥50 mL/min or serum creatinine ≤1.5 times the upper limit of normal.
⑧ Willing to participate in this study voluntarily, sign the informed consent form, and comply with the scheduled outpatient visits and related procedural requirements to complete follow-up.
Exclusion Criteria:
* In addition to a confirmed diagnosis of rectal cancer, there is a current or past history of active malignant tumors.
* Patients with metastases to other sites indicated by preoperative staging.
* Patients with suspicious positive lymph nodes in non-draining areas of the rectum, such as the internal and external iliac lymph nodes, as assessed by preoperative MRI or CT.
* Patients requiring emergency surgery due to complications such as intestinal obstruction, intestinal perforation, or intestinal hemorrhage.
* Patients with severe comorbid conditions and an estimated life expectancy of ≤5 years.
* Patients with known allergies to any components in the study.
⑦ Patients who have received immunosuppressive or systemic corticosteroid therapy for immunosuppressive purposes within 30 days prior to the initiation of study treatment.
⑧ Patients who have received any other investigational drug treatment (including immunotherapy) or participated in another interventional clinical trial within 30 days prior to screening.
⑨ Patients with other factors that may affect the study results or lead to premature termination of the study, such as alcoholism, drug abuse, other severe diseases requiring combined treatment (including psychiatric disorders), and severe laboratory abnormalities.
⑩ Patients with congenital or acquired immunodeficiency (such as HIV infection).
⑪ Vulnerable populations, including individuals with psychiatric disorders, cognitive impairments, critically ill patients, minors, pregnant women, illiterate individuals, etc.
⑫ Other circumstances where, in the investigator's judgment, the patient is deemed unsuitable to participate in the clinical trial.
Where this trial is running
Wenzhou, Zhejiang
- The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)
Study contacts
- Study coordinator: Yifei Pan, Master's Degree in Medicine
- Email: 13506641535@139.com
- Phone: 86 13506641535
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.