Starting soon
Phase 2
A Prospective, Multicenter, Single-Arm Phase II Exploratory Study of Serplulimab Combined With Oncolytic Virus H101, Short-Course Radiotherapy, and XELOX Chemotherapy as Total Neoadjuvant Treatment for Locally Advanced (cT1-3N0M0) Rectal Cancer
Condition(s) studied
Rectal NeoplasmsRectal Adenocarcinoma
Investigational drug(s) / intervention(s)
SerplulimabOncolytic Virus H101XELOX ChemotherapyShort-course Radiotherapy
Serplulimab: Serplulimab is a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1). It will be administered intravenously at a fixed dose of 300 mg on Day 1 of each 3-week cycle for a total of 6 cycles. Serplulimab is given in combination with chemotherapy, radiotherapy, and oncolytic virus therapy as part of total neoadjuvant treatment. The aim is to enhance anti-tumor immune response and improve treatment efficacy.
Oncolytic Virus H101: H101 is a recombinant human adenovirus type 5 oncolytic virus that selectively replicates in and lyses tumor cells while stimulating anti-tumor immune responses. It will be administered by intratumoral injection on Day 1 of Cycle 1 and Day 1 of Cycle 4. The dose will be determined based on tumor size. H101 is used in combination with immunotherapy, chemotherapy, and radiotherapy to enhance tumor cell killing and improve immune activation.
XELOX Chemotherapy: XELOX chemotherapy consists of oxaliplatin and capecitabine. Oxaliplatin will be administered intravenously at a dose of 130 mg/m² on Day 1, and capecitabine will be given orally at a dose of 1000 mg/m² twice daily from Day 1 to Day 14 of each 3-week cycle. A total of 6 cycles will be administered. Chemotherapy is combined with immunotherapy, radiotherapy, and oncolytic virus therapy to improve tumor response.
Short-course Radiotherapy: Short-course radiotherapy will be delivered to the rectal tumor using intensity-modulated radiation therapy (IMRT). The total dose is 25 Gy administered in 5 fractions over one week. Radiotherapy is given during the treatment course in combination with immunotherapy, chemotherapy, and oncolytic virus therapy. It aims to enhance local tumor control and stimulate anti-tumor immune response.
Study summary
This study aims to evaluate the safety and effectiveness of a combination treatment including a PD-1 inhibitor (serplulimab), oncolytic virus H101, short-course radiotherapy, and XELOX chemotherapy as total neoadjuvant therapy in patients with locally advanced low rectal cancer (cT1-3N0M0).
In this prospective, multicenter, single-arm phase II study, eligible patients will receive a standardized treatment regimen consisting of intratumoral injection of oncolytic virus H101, short-course radiotherapy, chemotherapy, and immunotherapy over multiple cycles. Tumor response will be assessed using imaging, endoscopy, and clinical evaluation after completion of treatment.
The primary objective is to determine the 1-year clinical complete response rate. Secondary outcomes include tumor response rate, organ preservation rate, survival outcomes, and treatment safety.
The results of this study may help improve treatment strategies for rectal cancer, increase the rate of complete response, and provide more opportunities for organ preservation while maintaining safety.
Eligibility
Inclusion Criteria:
\- Participants must meet all of the following criteria:
1. Age 18 to 80 years, male or female.
2. Histologically confirmed low rectal adenocarcinoma, with tumor located ≤5 cm from the anal verge.
3. Clinical stage T1-3N0M0 according to AJCC staging criteria.
4. Mismatch repair-proficient (pMMR) or microsatellite stable (MSS) tumor confirmed by immunohistochemistry or genetic testing.
5. No prior anti-tumor treatment.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, with an expected survival of at least 3 months.
7. Adequate organ function, including:
* Absolute neutrophil count ≥1.5 × 10\^9/L
* Platelet count ≥100 × 10\^9/L
* Hemoglobin ≥9 g/dL
* Serum albumin ≥3 g/dL
* Total bilirubin ≤1.5 × upper limit of normal (ULN)
* ALT and AST ≤2 × ULN
* Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min
* INR or PT ≤1.5 × ULN, and aPTT ≤1.5 × ULN
8. Thyroid function within normal range or adequately controlled.
9. Negative pregnancy test for women of childbearing potential.
10. Willingness to use effective contraception during the study and for 12 months after treatment.
11. Ability to understand and willingness to sign a written informed consent form.
12. Willingness and ability to comply with study procedures and follow-up.
Exclusion Criteria:
* Participants will be excluded if they meet any of the following criteria:
1. Histology other than rectal adenocarcinoma (e.g., gastrointestinal stromal tumor, lymphoma).
2. Prior pelvic radiotherapy.
3. Prior treatment with PD-1, PD-L1, or CTLA-4 inhibitors.
4. Known allergy to study drugs or their components.
5. History of other malignancies, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or papillary thyroid carcinoma.
6. Active autoimmune disease or history of autoimmune disease requiring systemic treatment.
7. Immunodeficiency, including HIV infection, or history of organ transplantation.
8. History of interstitial lung disease or non-infectious pneumonitis.
9. Active tuberculosis infection or history of untreated tuberculosis.
10. Active hepatitis B or hepatitis C infection.
11. Severe cardiovascular, pulmonary, or renal disease.
12. Uncontrolled hypertension despite medication.
13. History of substance abuse (alcohol or drugs).
14. Active uncontrolled infection.
15. Use of systemic immunosuppressive therapy.
16. Pregnant or breastfeeding women.
17. Any condition that, in the investigator's opinion, may interfere with study participation or safety.
Primary outcome measure(s)
- 1-year Clinical Complete Response Rate — 1 year after completion of treatment
Clinical complete response (cCR) is defined as no evidence of residual tumor based on digital rectal examination, endoscopy showing mucosal healing or scar, and imaging (MRI or CT) without tumor signal or metabolic activity, and no distant metastasis. The proportion of patients achieving cCR and maintaining it for at least 1 year will be evaluated.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Chongqing University Cancer Hospital |
Chongqing |
Chongqing Municipality |
|
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