Short-course pelvic radiotherapy followed by CAPOX (capecitabine + oxaliplatin) and bevacizumab, with or without PD‑1 immunotherapy, for locally advanced rectal cancer.

Short-Course Radiotherapy Combined With CAPOX and Bevacizumab, With or Without PD-1 Inhibitors, as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

This trial tests whether adding a PD‑1 immunotherapy to short-course radiotherapy followed by CAPOX and bevacizumab helps adults with locally advanced rectal cancer get a higher complete response rate and fewer distant metastases.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 104 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, bevacizumab
• Locations: 1 site (Shanghai)
• Trial ID: NCT07198165 on ClinicalTrials.gov

What this trial studies

This Phase 2 trial gives patients short-course radiotherapy (SCRT) and then systemic chemotherapy with CAPOX plus bevacizumab, with randomization or assignment to receive a PD‑1 inhibitor or not as part of total neoadjuvant therapy. Eligible patients are adults with untreated locally advanced rectal adenocarcinoma defined by MRI criteria (T3c‑T4, N2, EMVI+, MRF+, or low‑lying tumors not suitable for sphincter preservation) and adequate organ function. Patients with BRAF mutations or MSI‑high tumors are excluded, and standard imaging is used to rule out distant metastases before enrollment. Primary goals include improving complete response and local control while monitoring safety and distant metastasis rates.

Who should consider this trial

Good fit: Adults 18–75 with previously untreated locally advanced rectal adenocarcinoma meeting specified MRI risk features, ECOG 0–1, adequate organ function, and no BRAF mutation or MSI‑high status are ideal candidates.

Not a fit: Patients with BRAF mutations, MSI‑high tumors, distant metastases, severe intestinal obstruction, poor performance status, or inadequate organ function are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding PD‑1 immunotherapy could raise complete response rates and reduce distant spread, possibly increasing organ preservation and improving long‑term outcomes.

How similar studies have performed: PD‑1 inhibitors have clear efficacy in MSI‑high colorectal cancer, but combining immunotherapy with chemoradiation in microsatellite‑stable locally advanced rectal cancer is a newer approach with limited early‑phase data showing mixed but encouraging signals.

Eligibility criteria

Inclusion Criteria:

* Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
* Exclusion of patients with BRAF mutations or MSI-H status, as determined by pre-enrollment genetic testing including RAS, BRAF, and MSI analysis. RAS mutation status is permitted regardless.
* Absence of severe intestinal obstruction symptoms and no evidence of distant metastasis confirmed by imaging examinations such as CT, MRI, or PET/CT.
* Confirmation as locally advanced rectal cancer by rectal MRI, meeting one or more of the following criteria: T3c-d or T4, N2, EMVI(+), MRF(+), lateral lymph node metastasis; or patients with low-lying rectal cancer (≤5 cm from the anal verge) unsuitable for sphincter-preserving surgery prior to neoadjuvant therapy.
* Age 18 to 75 years.
* ECOG Performance Status of 0 to 1, without severe comorbid medical conditions.
* Adequate organ function:

Hematopoietic: Hemoglobin ≥90 g/L, Platelets ≥80 × 10\^9/L, Absolute Neutrophil Count ≥1.5 × 10\^9/L.

Hepatic: ALT and AST \< 2.5 × ULN. Renal: Serum Creatinine \< 1.5 × ULN.

* Provision of signed and dated written informed consent.

Exclusion Criteria:

* Patients found to have BRAF mutations or MSI-H status.
* Patients who have previously received chemotherapy, radiotherapy, immunotherapy, targeted therapy, or surgical resection for colorectal cancer prior to enrollment.
* History or presence of another malignancy (except for early-stage basal cell carcinoma or carcinoma in situ of the cervix) within the past 3 years, with the disease not under control.
* Patients who are pregnant (confirmed by serum or urine β-HCG test) or breastfeeding.
* Patients with severe cardiac, hepatic, renal, neurological, or psychiatric diseases.
* Patients with active infections.
* Poor overall health status, with an ECOG performance status ≥2.
* Patients who have undergone organ transplantation requiring immunosuppressive therapy, or those requiring long-term corticosteroid treatment for autoimmune diseases.
* Patients with comorbid conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the completion of the study.
* Known hypersensitivity to any of the study drugs.

Where this trial is running

Shanghai

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Bo Feng

Conditions Rectal Cancer; Rectal Adenocarcinoma; Rectal Cancer, Radiotherapy; Rectal Cancer Patients; Immunotherapy; Total Neoadjuvant Therapy; Total Neoadjuvant Treatment; Targeted Therapy