Short-Course Online Adaptive Radiotherapy Combined With Chemotherapy, Targeted Therapy and Immunotherapy as Total Neoadjuvant Therapy (TNT) for Locally Advanced Rectal Cancer

NCT07581626 | Not Yet Recruiting Phase 2

• 1 other identifier: KL-A140-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Standard treatment for patients with proficient mismatch repair (pMMR) / microsatellite stable (MSS) locally advanced rectal cancer (LARC) consists primarily of neoadjuvant chemoradiotherapy followed by radical surgery. Several studies (including the UNION, STELLAR, TORCH, and SPRING-01 trials, etc) have demonstrated that the neoadjuvant strategy of short-course radiotherapy followed by chemotherapy combined with immunotherapy can improve pCR rate in patients with pMMR/MSS LARC, and might also provide higher organ preservation rates and long-term survival benefits. The study aims to explore the efficacy and safety of a TNT regimen comprising short-course radiotherapy combined with chemotherapy, cetuximab N01 (for patients with wild-type RAS/BRAF) or bevacizumab (for patients with mutant RAS/BRAF), and sintilimab in patients with high-risk LARC.

Conditions

Locally Advanced Rectal Cancer (LARC)

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR)

  CR = Pathological Complete Response (pCR) + Clinical Complete Response (cCR)

  Within 3 months after surgery

Secondary Outcomes (8)

• R0 resection rate

  Within 3 months after surgery

• LER

  Within 3 months after surgery

• ORR

  Around 6 months after recruitment

• DCR

  Around 6 months after recruitment

• 3y-EFS

  Around 3 years after recruitment

Study Arms (1)

SCRT+Sintilimab+Cetuximab N01/Bevacizumab+mFOLFOX6/CAPOX

EXPERIMENTAL

Drug: SCRT+targeted therapy+immunotherapy+chemotherapy

Interventions

SCRT+targeted therapy+immunotherapy+chemotherapy DRUG

SCRT: 25 Gy, 5 Gy × 5 fr. One week after completion of SCRT: 1. Patients with wild-type RAS/BRAF: mFOLFOX6: oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² IV bolus on Day 1; followed by 5-fluorouracil 2400 mg/m² continuous infusion over 46 hours, q2w; sintilimab 200 mg/m² IV infusion on Day 1, q3w; cetuximab N01 500 mg/m² IV infusion on Day 1, q2w; Combination therapy for 18 weeks (9 cycles of chemotherapy). 2. Patients with mutant RAS/BRAF: CAPOX: oxaliplatin 130 mg/m² IV ivgtt, D1; capecitabine 1000 mg/m² BID, po, D1-14, q3w, for 6 cycles; sintilimab 200 mg/m² ivgtt, D1, q3w, for 6 cycles; bevacizumab 7.5 mg/kg IV infusion on Day 1, q3w, for 5 cycles

SCRT+Sintilimab+Cetuximab N01/Bevacizumab+mFOLFOX6/CAPOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signed the informed consent form.
• Aged 18-75 years (inclusive of 18 and 75 years).
• pMMR/MSS.
• Middle or low rectal cancer located ≤10 cm from the anal verge as assessed by MRI.
• Histopathologically confirmed locally advanced rectal adenocarcinoma and high-risk features confirmed by pelvic MRI (meeting any of the following criteria: clinical stage cT3N+ or cT4N0/+; MRF+ or EMVI+; enlarged lateral pelvic lymph nodes).
• ECOG PS of 0-1.
• Expected survival ≥2 years.
• No prior anti-tumor therapy.
• At least one measurable lesion with a longest diameter ≥10 mm measured by MRI (by RECIST version 1.1).
• Organ functions meeting the following requirements (no blood products or cell growth factors allowed within 14 days prior to enrollment):
• Absolute neutrophil count ≥1.5×10⁹/L; Platelet count ≥100×10⁹/L; Hemoglobin ≥90 g/L; Total bilirubin \<1.5×ULN; ALT and/or AST \<2.5×ULN; Serum creatinine \<1.5×ULN; Creatinine clearance ≥50 mL/min.
• Women of childbearing potential must use effective contraceptive measures.
• Good compliance and willingness to comply with follow-up requirements.

You may not qualify if:

• Unable to comply with the study protocol or study procedures.
• Patients with contraindications to surgery.
• Patients with metastatic disease or recurrent rectal cancer.
• Uncontrolled active autoimmune disease or active inflammatory disease at enrollment, or receiving immunosuppressive therapy.
• History of organ transplantation.
• Known interstitial lung disease (ILD) or unexplained persistent cough and dyspnea.
• Patients with familial adenomatous polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), active Crohn's disease, or active ulcerative colitis.
• Other malignancy diagnosed within 5 years prior to enrollment, except for radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Severe cardiovascular disease within 6 months prior to enrollment, including unstable angina pectoris or myocardial infarction.
• Subjects with hypersensitivity to the investigational product or any of its excipients.
• Participation in another clinical trial of an unapproved/investigational drug within 4 weeks prior to enrollment and having received the corresponding investigational product.
• Clinically significant electrolyte abnormalities judged by the investigator.
• Uncontrolled hypertension prior to enrollment, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg despite medication.
• Poorly controlled diabetes mellitus prior to enrollment (fasting glucose concentration ≥ CTCAE Grade 2 after standard treatment).
• Any disease or condition affecting drug absorption prior to enrollment, or inability of the patient to take oral medication.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

China PLAGH

Beijing, China

Location

Central Study Contacts

Guanghai Dai, MD

CONTACT

+86 13801232381; 463043539@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 12, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)