Rectal Cancer
Conditions
Keywords
lymph-node-sparing short-course radiotherapy, capecitabine, PD-1 inhibitor, CTLA-4 inhibitor, organ preservation, clinical complete response
Brief summary
This is a single-arm, prospective, multicenter study evaluating a novel neoadjuvant treatment strategy for patients with early, mid-low rectal adenocarcinoma that is microsatellite stable (MSS). Instead of irradiating regional lymph nodes, we deliver short-course radiotherapy (25 Gy in 5 fractions) exclusively to the primary tumor (lymph-node-sparing approach), immediately followed by four 3-week cycles of capecitabine plus combined PD-1/CTLA-4 immune checkpoint inhibitors. Two weeks after completing chemo-immunotherapy, tumor response is assessed. Patients who achieve a clinical complete response may enter a watch-and-wait program; others will undergo local excision or total mesorectal excision (TME) as appropriate. The primary endpoint is the rate of complete response (clinical and pathological). Secondary endpoints include organ-preservation rate, 3-year local recurrence, 3-year disease-free and overall survival, toxicity, and quality-of-life measures. Results from a pilot study suggest that this regimen may substantially improve complete response rates while reducing radiation-related toxicity, potentially allowing more patients to avoid radical surgery and permanent stoma.
Interventions
RADIATIONLymph-node-sparing short-course radiotherapy
Three-dimensional conformal or intensity-modulated radiotherapy targeting only the primary tumor bed (no regional lymph nodes), delivering a total dose of 25 Gy in 5 Gy fractions over five consecutive days.
DRUGCapecitabine
Oral capecitabine 1,000 mg/m² administered twice daily on Days 1-14 of each 21-day cycle, for a total of four cycles.
DRUGPD-1/CTLA-4 inhibitor (Aiparolitoworixureli injection)
Intravenous PD-1/CTLA-4 bispecific monoclonal antibody at 5 mg/kg every 3 weeks for four cycles, starting on Day 8 after completion of radiotherapy.
Sponsors
Sir Run Run Shaw Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy. 2. Male or Female aged 18-80. 3. Patients diagnosed with low rectal cancer within 7 cm from the lower edge of the tumor to the anal verge by pelvic MRI and rectal ultrasound, the clinical stage is cT2-3N0M0. 4. Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive. 5. Eastern Cooperative Oncology Group (ECOG) score 0-1. 6. No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation). 7. Informed consent form signed.
Exclusion criteria
1. Patients with a previous history of malignant tumors besides rectal cancer. 2. Patients with distant metastases before enrollment. 3. Patients with metastatic regional or non-regional lymph nodes are assessed by MRI or CT. 4. Patients with obstruction, perforation, or bleeding that require emergency surgery. 5. Patients with severe concomitant diseases and estimated survival time ≤ 5 years. 6. Allergic to any component of the therapy. 7. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy. 8. Contraindications to radiotherapy and chemotherapy. 9. Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening. 10. Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities. Patients with congenital or acquired immune deficiency (such as HIV infection). 11. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc. Other conditions that investigators consider not suitable for this study. 12. Patient not suitable for participating by other concerns of researchers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and pathological complete response rate (CR rate) | Up to 12 weeks after completion of chemo-immunotherapy | Proportion of enrolled patients who achieve a clinical complete response (cCR) on imaging, endoscopy, and biopsy and/or a pathological complete response (pCR) in surgical specimens (if resected) following lymph-node-sparing short-course radiotherapy combined with capecitabine and PD-1/CTLA-4 inhibitor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Organ preservation rate | 1 year after enrollment | Proportion of patients who avoid total mesorectal excision (TME) and permanent stoma by remaining in watch-and-wait or undergoing only local excision. |
| 3-year local recurrence rate | 3 years | Proportion with tumor recurrence in the pelvis |
| Overall survival(OS） | 3 years after chemotherapy or surgery | The three-year overall survival of patients. |
| Adverse effects rate | From date of initiation of treatment until the date of death from any cause, assessed up to 3 years | Rate of radiotherapy, chemotherapy and immunotherapy related adverse events |
Countries
China
Contacts
Primary ContactBingjun Bai, MD
Outcome results
None listed