Short-Course Radiotherapy, Nal-IRI, Capecitabine, and Camrelizumab for Locally Advanced MSS Rectal Cancer

NCT07521605 | Not Yet Recruiting Phase 2

• 1 other identifier: neoNRCC
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for adults with locally advanced rectal cancer that has not spread to distant organs, and is classified as pMMR or MSS (which means it typically does not respond well to immunotherapy alone). The purpose is to see if a new combination of treatments given before surgery (neoadjuvant therapy) can more effectively shrink the tumor and increase the chance of curing the cancer or avoiding surgical removal of the rectum. The main things you will do in this study are:

1. 1.Receive a Short Course of Radiation Therapy (5 treatments over 1 week).
2. 2.After a 1-week break, receive a combination of three drugs:
3. 3.No sign of cancer cells in the surgically removed tissue (Pathological Complete Response, pCR), or
4. 4.No sign of cancer can be found through clinical exams, scans, and scopes, allowing the patient to avoid immediate surgery under a "Watch and Wait" strategy (Clinical Complete Response, cCR).
5. 5.The safety of the treatment and its side effects.
6. 6.How well the cancer is controlled over time (e.g., 3-year survival without cancer recurrence).
7. 7.The rate of successful tumor removal and the rate of preserving the anus.

Conditions

Rectal Cancer Patients

Keywords

Locally advanced rectal cancer; pMMR/MSS; Short-course radiotherapy; Liposomal irinotecan; Neoadjuvant immunochemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  The primary endpoint is the Complete Response (CR) rate after completion of neoadjuvant therapy, which is a composite of pathological complete response (pCR) and clinical complete response (cCR). 1. pCR is defined as the absence of viable tumor cells in the surgical specimen (TRG1a according to the Becker tumor regression grading system) in patients who undergo surgery. 2. cCR is defined as the achievement of a ycT0N0 status, assessed by clinical evaluations (including digital rectal exam, endoscopy, MRI, etc.), in patients who enter a "Watch and Wait" strategy without immediate surgery.

  From the start of treatment until approximately 2 weeks after the completion of all neoadjuvant therapy, assessed over a period of approximately 24-26 weeks.

Secondary Outcomes (7)

• 3 year Disease-Free Survival

  3 years from the start of treatment.

• 3 year Overall Survival

  3 years from the start of treatment.

• Objective Response Rate

  From the start of treatment until approximately 2 weeks after the completion of all neoadjuvant therapy, assessed over a period of approximately 24-26 weeks.

• R0 Resection Rate

  Assessed at the time of surgery following neoadjuvant therapy, over a period of approximately 24-30 weeks from the start of treatment.

• Tumor Regression Grade

  Assessed during pathological evaluation after surgery, over a period of approximately 24-30 weeks from the start of treatment.

Study Arms (1)

Neoadjuvant Therapy Arm

EXPERIMENTAL

Radiation: Short-Course Radiotherapy; Drug: Liposomal Irinotecan (nal-IRI); Drug: Capecitabine; Drug: Camrelizumab

Interventions

Short-Course Radiotherapy RADIATION

Short-course radiotherapy is a radiation therapy regimen delivered over a condensed period. In this study, patients will receive a total dose of 25 Gray (Gy), administered in 5 fractions (5 Gy per fraction), delivered once daily over five consecutive days. This intervention constitutes the initial phase of the neoadjuvant treatment protocol.

Neoadjuvant Therapy Arm

Liposomal Irinotecan (nal-IRI) DRUG

Liposomal irinotecan is a nanoliposomal formulation of the chemotherapeutic agent irinotecan, designed to enhance tumor drug delivery and reduce systemic toxicity. In this study, it will be administered intravenously at a dose of 60 mg/m² on Day 1 of each 21-day cycle, for a total of 8 cycles, following the completion of short-course radiotherapy.

Neoadjuvant Therapy Arm

Capecitabine DRUG

Capecitabine is an oral fluoropyrimidine carbamate prodrug that is converted to 5-fluorouracil in the body. In this study, it will be administered orally at a dose of 1000 mg/m² twice daily (BID) from Days 1 to 14 of each 21-day cycle, for a total of 8 cycles, in combination with liposomal irinotecan and camrelizumab.

Neoadjuvant Therapy Arm

Camrelizumab DRUG

Camrelizumab is a humanized monoclonal antibody that targets the programmed cell death-1 (PD-1) receptor on immune cells, functioning as an immune checkpoint inhibitor. In this study, it will be administered intravenously at a fixed dose of 200 mg on Day 1 of each 21-day cycle, for a total of 8 cycles, in combination with liposomal irinotecan and capecitabine.

Neoadjuvant Therapy Arm

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 75 years, male or female.
• Histologically confirmed diagnosis of rectal adenocarcinoma.
• Confirmed mismatch repair proficient (pMMR) or microsatellite stable (MSS) status by immunohistochemistry or PCR methods.
• Locally advanced disease assessed by pelvic MRI, classified as cT3-4aN0M0 or any T stage with node-positive (N+) disease, without distant metastasis (M0), according to the AJCC 8th edition staging system.
• The lower edge of the tumor is located within 10 cm from the anal verge (defined as low/mid rectal cancer).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, hepatic, and renal function, defined as: Absolute Neutrophil Count (ANC) ≥ 1.5 x 10⁹/L，Platelet count ≥ 100 x 10⁹/L，Hemoglobin ≥ 90 g/L，Total Bilirubin ≤ 1.5 times the Upper Limit of Normal (ULN)，Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 x ULN，Serum creatinine ≤ 1.5 x ULN or Creatinine Clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula)
• Voluntarily participates in the study, signs the informed consent form, demonstrates good compliance, and is able to cooperate with follow-up procedures.

You may not qualify if:

• Evidence of distant metastasis (M1 disease) on baseline imaging.
• Previous radiotherapy to the pelvis, or any prior systemic chemotherapy, targeted therapy, or immunotherapy for colorectal cancer.
• History of other active malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or other localized tumors considered cured by local treatment.
• Any of the following uncontrolled conditions or comorbidities:
• ）Severe active infection requiring systemic therapy. 2）Unstable angina, myocardial infarction, or congestive heart failure (NYHA Class II-IV) within the last 6 months.
• ）Uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders that would compromise the ability to provide informed consent or comply with study procedures.
• \. Known history of severe immunodeficiency or active autoimmune disease requiring systemic immunosuppressive therapy (e.g., corticosteroids at doses \> 10mg/day prednisone equivalent) within the past 2 years.
• \. Known history of hypersensitivity to any component of the study drugs (Liposomal Irinotecan, Capecitabine, Camrelizumab) or history of severe hypersensitivity reactions to other monoclonal antibodies.
• \. Pregnant or lactating women, or subjects of childbearing potential who are unwilling to use highly effective contraception during the study period and for at least 6 months after the last dose of study treatment.
• \. Any other condition or circumstance that, in the opinion of the investigator, would compromise the patient's safety or adherence to the protocol (e.g., inability to swallow oral medications, active gastrointestinal bleeding, intestinal obstruction).

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510000, China

Location

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MeSH Terms

Interventions

irinotecan sucrosofate; Capecitabine; camrelizumab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Deqing Wu, Dr.

CONTACT

020 83827812 60910; wudeqing@gdph.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: single-arm phase II trial
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: April 13, 2026
• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2034
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CN (1)