Optimizing immunotherapy with pre-surgery chemotherapy and radiation for locally advanced rectal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 2 interventional trial compares different ways of combining the PD-1 inhibitor sintilimab with total neoadjuvant therapy (TNT) for clinical stage II/III rectal adenocarcinoma that is microsatellite-stable (MSS) or mismatch-repair proficient (pMMR). The study varies the timing of radiotherapy versus chemotherapy, the number of chemotherapy cycles (CAPOX), and the radiotherapy approach (short-course vs long-course concurrent chemoradiotherapy) alongside immunotherapy to find an optimal regimen. Participants receive preoperative systemic and local treatments intended to maximize tumor regression before planned surgery. Outcomes focus on tumor response rates and the potential for organ-preserving approaches.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age 18-75 years, regardless of gender;
2. Pathologically confirmed rectal adenocarcinoma with immunohistochemical results indicating pMMR (proficient mismatch repair) or genetic testing confirming MSS (microsatellite stability);
3. Staged as clinical stage II/III (cT3-T4N0 or cT2-4N+, no distant metastasis, per the 8th Edition AJCC Cancer Staging Manual, 2018) via MRI or endoscopic ultrasound, and meeting any one of the following:

   * cT3 with tumor inferior margin ≤ 6 cm from the anal verge;

     * cT3c/d with tumor inferior margin ≥ 6-12 cm from the anal verge; ③ cN2; ④ cT4; ⑤ MRF+ (mesorectal fascia involvement); ⑥ EMVI+ (extramural vascular invasion);
4. ECOG performance status 0-1;
5. Meeting basic laboratory criteria (e.g., hematologic, hepatic, and renal function);
6. No history of hypersensitivity to 5-Fu-based agents or platinum-based drugs;
7. Patients with primary rectal cancer must have received no prior surgery (excluding palliative colostomy), chemotherapy, or other antitumor therapies from diagnosis to enrollment;
8. No prior radiation to the planned radiotherapy site;
9. Signed informed consent form.

Exclusion Criteria:

1. Prior treatment with anti-PD-1/L1 and/or anti-CTLA-4 immunotherapy or other investigational immunotherapeutic agents;
2. History of severe autoimmune diseases, including active inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g., granulomatosis with polyangiitis);
3. Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis;
4. Risk factors for bowel perforation, such as active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis, or other known predisposing conditions;
5. History of other malignancies, except for cured non-melanoma skin cancer or cervical carcinoma in situ;
6. Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or uncontrolled arrhythmia;
7. Physical examination findings or clinical laboratory abnormalities deemed by the investigator to interfere with study outcomes or increase treatment-related risks, or other uncontrolled comorbidities;
8. Pregnant or breastfeeding women;
9. Congenital or acquired immunodeficiency disorders, including HIV infection, or history of organ/stem cell transplantation;
10. Active hepatitis B (HBV-DNA ≥2000 U/mL), hepatitis C (HCV), or active tuberculosis infection;
11. Prior administration of cancer vaccines or receipt of any vaccine within 4 weeks before treatment initiation (Note: Seasonal inactivated influenza vaccines are permitted; live-attenuated intranasal vaccines are prohibited);
12. Concurrent use of immunomodulators, chemotherapy, investigational drugs, or long-term corticosteroids (≥10 mg/day prednisone equivalent);
13. Patients with psychiatric disorders, substance abuse, or social circumstances that may compromise compliance, as assessed by the investigator;
14. Hypersensitivity or contraindications to the study medications.

Where it's running

• Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
  Beijing, China Recruiting
• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen
  Shenzhen, China Recruiting

Study contacts

• Study coordinator: Yuan Tang
• Email: tangyuan82@126.com
• Phone: +86-15011304945

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• NeoCSR-Omics: CAPOX and Serplulimab Before or After Short-Course RT in Locally Advanced Rectal Cancer

  This trial tests whether giving CAPOX chemotherapy with the PD-1 blocker serplulimab before or after short-course radiotherapy helps people with locally advanced rectal cancer achieve complete clinical or pathological responses.

  Recruiting Phase 2 Chongqing University Cancer Hospital · Chongqing, Chongqing Municipality · NCT07898865

• Personalized blood ctDNA-MRD multi-omics test to predict neoadjuvant therapy response in rectal cancer

  This project will test whether a personalized blood-based ctDNA-MRD multi-omics test can predict how well neoadjuvant therapy works for people with locally advanced rectal cancer.

  Recruiting Beijing Friendship Hospital · Beijing, Beijing Municipality · NCT07393048

• Short-course radiotherapy plus CAPOX chemotherapy with serplulimab and bevacizumab for mid-low MSS rectal cancer

  This trial will try short-course radiotherapy followed by CAPOX chemotherapy together with serplulimab and bevacizumab before surgery in people with mid-low MSS locally advanced rectal cancer to see if it is safe and shrinks tumors.

  Recruiting Phase 2 First Affiliated Hospital of Wenzhou Medical University · Wenzhou, Zhejiang · NCT07347951

• Neoadjuvant dostarlimab for locally advanced dMMR/MSI‑H rectal cancer in routine practice

  This project will try neoadjuvant dostarlimab in adults with dMMR/MSI‑H stage II–III rectal cancer to see how well it works and how safe it is in real-world clinical care.

  Recruiting National Cancer Institute, Naples · Naples and 1 other locations · NCT07269249

• Personalized long-course radiotherapy and chemotherapy, with or without immunotherapy, for locally advanced rectal cancer

  This study tests whether adding the immunotherapy drug serplulimab to personalized long-course radiotherapy and chemotherapy helps adults with locally advanced rectal cancer achieve complete tumor disappearance.

  Recruiting Phase 3 West China Hospital · Chengdu, Sichuan · NCT07020247

• Adding the immunotherapy drug tislelizumab to total neoadjuvant treatment for locally advanced rectal cancer

  This trial will test whether giving the immunotherapy drug tislelizumab together with total neoadjuvant treatment helps people with locally advanced rectal cancer avoid major surgery.

  Recruiting Phase 2 Rabin Medical Center · Mainz and 1 other locations · NCT06940388

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.