Involved-field radiotherapy with total neoadjuvant chemotherapy and PD-1 inhibitor for pMMR locally advanced rectal cancer

Clinical Exploration of Involved-field Radiotherapy-TNT Combined With PD-1 Inhibitor for pMMR Locally Advanced Rectal Cancer: a Prospective, Open-label, Randomized Controlled Trial (Neo-Field I)

This trial tests whether adding the PD‑1 drug camrelizumab to involved-field radiotherapy and total neoadjuvant chemotherapy (capecitabine or CAPOX) improves tumor response and is safe for adults with pMMR locally advanced rectal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hebei Medical University Fourth Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shijiazhuang)
• Trial ID: NCT07057089 on ClinicalTrials.gov

What this trial studies

This phase II, single-center trial in Shijiazhuang, China combines involved-field radiotherapy (including elective nodal irradiation) with total neoadjuvant chemotherapy (capecitabine or CAPOX) and the PD‑1 inhibitor camrelizumab in patients with pathologically confirmed pMMR rectal adenocarcinoma. Eligible adults have clinical stage cT3–4NanyM0 or cT1–2N+M0, tumors within 10 cm of the anal verge or below the peritoneal reflection, ECOG 0–1, and adequate blood, liver, kidney, and coagulation function. Participants receive coordinated radiotherapy and systemic therapy followed by planned assessment of tumor response, surgical outcomes, and treatment-related adverse events. The trial aims to generate efficacy and safety signals to inform whether this combination merits further study.

Who should consider this trial

Good fit: Adults (≥18 years) with pathologically confirmed pMMR rectal adenocarcinoma staged cT3–4NanyM0 or cT1–2N+M0, ECOG 0–1, tumor ≤10 cm from the anal verge or below the peritoneal reflection, and adequate laboratory and organ function are the intended participants.

Not a fit: Patients with dMMR/MSI‑high tumors, distant metastatic disease, poor performance status, significant organ dysfunction, or inability to attend the single center in Shijiazhuang are unlikely to benefit from or be eligible for this protocol.

Why it matters

Potential benefit: If successful, this approach could increase preoperative tumor response rates and potentially allow more organ-preserving surgeries for people with pMMR locally advanced rectal cancer.

How similar studies have performed: Immunotherapy is effective in dMMR/MSI‑high colorectal cancer and early studies combining radiotherapy with PD‑1 inhibitors show promise in several cancers, but strong evidence of benefit in pMMR locally advanced rectal cancer is currently limited.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
3. Pathologic diagnosis of adenocarcinoma of the rectum, definite pMMR type;
4. Clinical staging of T3-4NanyM0 or T1-2N+M0 (based on AJCC 8th edition staging criteria);
5. The lower margin of the primary tumor is located below the peritoneal reflex or the lower margin of the tumor is ≤10 cm from the anal verge;
6. Pre-enrollment laboratory indicators meet the following indicator ranges： 1)Blood: absolute neutrophils ≥1.5×10\^9/L, platelets ≥100×10\^9/L, hemoglobin ≥90g/L; 2)Liver and kidney function: ALT/AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60mL/min (Cockcroft-Gault formula)； 3)Coagulation: INR ≤ 1.5, APTT ≤ 1.5 x ULN (for those not receiving anticoagulation)；
7. Women or men of childbearing potential need to agree to use effective contraception during the study and for 6 months after the last treatment session;
8. Voluntary written informed consent and commitment to complete the full treatment and follow-up program.

Exclusion Criteria:

1. Pathologic type is other specific types such as neuroendocrine carcinoma, squamous carcinoma, etc;
2. Previous radiotherapy, chemotherapy, targeted or immunotherapy for rectal cancer;
3. Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy)；
4. Presence of active infection (e.g. HIV, HBV/HCV viral load positive requiring stabilization on antiretroviral therapy)；
5. Severe cardiovascular disease (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension \>160/100 mmHg)；
6. History of other malignant tumors (except non-melanoma skin cancers, cervical cancer in situ, etc. cured for ≥5 years)；
7. Uncontrolled diabetes mellitus (HbA1c \> 8%), abnormal thyroid function (TSH outside normal range and requiring pharmacologic intervention)；
8. Severe chronic bowel disease (e.g., Crohn's disease, active ulcerative colitis)； Patients deemed by the investigator to be unsuitable for participation in this study.

Where this trial is running

Shijiazhuang

• the Fourth Hospital of Hebei Medical University — Shijiazhuang, China (Recruiting)

Study contacts

• Principal investigator: Fengpeng Wu — Hebei Medical University Fourth Hospital
• Study coordinator: Fengpeng Wu, Professor

Conditions Locally Advanced Rectal Cancer