Node-sparing short-course radiation with capecitabine plus PD-1/CTLA-4 immunotherapy for early rectal cancer

Node-Sparing Short-Course Radiation Combined With Capecitabine and PD-1/CTLA-4 for MSS Early Middle and Low Rectal Cancer (mRCAT-E): An Open-label, Single-arm, Prospective Multicenter Clinical Trial

This treatment will try giving short-course radiation just to the tumor followed by capecitabine and combined PD-1/CTLA-4 immunotherapy for people with early, microsatellite-stable rectal cancer who want to preserve their anus.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sir Run Run Shaw Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07068763 on ClinicalTrials.gov

What this trial studies

This single-arm Phase 2 study delivers short-course, lymph-node-sparing radiotherapy (25 Gy in 5 fractions) to the primary tumor, immediately followed by four 3-week cycles of capecitabine combined with a PD-1 plus CTLA-4 inhibitor (Aiparolitoworixureli). Two weeks after completing chemo-immunotherapy, tumor response is assessed and patients with a clinical complete response may enter a watch-and-wait program while others proceed to local excision or total mesorectal excision as clinically indicated. The primary endpoint is complete response rate (clinical and pathological), and secondary endpoints include organ-preservation rate, 3-year local recurrence, 3-year disease-free and overall survival, toxicity, and quality-of-life. The trial enrolls treatment-naïve adults aged 18–80 with low (≤7 cm from the anal verge) cT2–3N0M0 MSS/pMMR rectal adenocarcinoma and ECOG 0–1 at Sir Run Run Shaw Hospital.

Who should consider this trial

Good fit: Ideal candidates are treatment-naïve adults 18–80 with low (≤7 cm) cT2–3N0M0 rectal adenocarcinoma that is MSS/pMMR, ECOG 0–1, who strongly wish to pursue anal preservation.

Not a fit: Patients with regional or distant lymph node or distant metastases, prior pelvic radiation or other prior malignancies, bowel obstruction or perforation, or those unwilling to pursue organ preservation are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase the chance of avoiding major rectal surgery and preserve the anus while maintaining cancer control.

How similar studies have performed: Prior neoadjuvant and organ-preservation trials have shown promise combining short-course radiotherapy with chemotherapy and some early pilot data support adding immunotherapy, but lymph-node-sparing radiation plus combined PD-1/CTLA-4 in MSS rectal cancer is largely novel with limited published outcomes.

Eligibility criteria

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.

Where this trial is running

Hangzhou, Zhejiang

• Sir run run shaw hospital — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Bingjun Bai, MD

Conditions: Rectal Cancer, lymph-node-sparing short-course radiotherapy, capecitabine, PD-1 inhibitor, CTLA-4 inhibitor, organ preservation, clinical complete response