Short-Course Radiotherapy Followed by Liposomal Irinotecan, Capecitabine, and Camrelizumab as Neoadjuvant Therapy for Locally Advanced pMMR/MSS Low Rectal Cancer: A Prospective Single-Arm Phase II Trial Protocol
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Complete Response Rate
Study Overview
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:
- Receive a Short Course of Radiation Therapy (5 treatments over 1 week).
- After a 1-week break, receive a combination of three drugs:
1）Nal-IRI (a special form of the chemotherapy drug Irinotecan, designed to have fewer side effects) 2）Capecitabine (a chemotherapy pill) 3）Camrelizumab (an immunotherapy drug) 3. This drug combination is given in 8 cycles, with each cycle lasting 3 weeks. 4. After finishing all cycles, the doctors will carefully check how the tumor responded.
The most important goal of this research is to see how many patients achieve a "Complete Response," which means:
- No sign of cancer cells in the surgically removed tissue (Pathological Complete Response, pCR), or
- 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).
Researchers will also monitor:
- The safety of the treatment and its side effects.
- How well the cancer is controlled over time (e.g., 3-year survival without cancer recurrence).
- The rate of successful tumor removal and the rate of preserving the anus.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
single-arm phase II trial
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- •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:
- •1）Severe active infection requiring systemic therapy. 2）Unstable angina, myocardial infarction, or congestive heart failure (NYHA Class II-IV) within the last 6 months.
- •3）Uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders that would compromise the ability to provide informed consent or comply with study procedures.
- •5. 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.
- •6. 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.
- •7. 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.
- •8. 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).
Arms & Interventions
Neoadjuvant Therapy Arm
Intervention: Short-Course Radiotherapy (Radiation)
Neoadjuvant Therapy Arm
Intervention: Liposomal Irinotecan (nal-IRI) (Drug)
Neoadjuvant Therapy Arm
Intervention: Capecitabine (Drug)
Neoadjuvant Therapy Arm
Intervention: Camrelizumab (Drug)
Outcomes
Primary Outcomes
Complete Response Rate
Time Frame: 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.
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.
Secondary Outcomes
- 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.)
- Sphincter Preservation Rate(Confirmed immediately after surgery, over a period of approximately 24-30 weeks from the start of treatment.)
- Incidence of Treatment-Related Adverse Events(From the time of informed consent until 30 days after the last dose of study treatment, assessed over a period of approximately 28-31 weeks.)