mRCAT: Nodes-sparing Short-course Radiation Combined With CAPOX and Tislelizumab for MSS Middle and Low Rectal Cancer
Study Details
Study Description
Brief Summary
This is an open-label, prospective, multicenter phase II clinical trial to evaluate modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) for patients with MSS middle and low rectal cancer. A total of 32 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The organ preservation rate, tumor regression grade, long-term prognosis, and adverse effects will also be analyzed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm Participants will receive 5*5Gy modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 3 cycles, followed by total mesorectal excision surgery. |
Radiation: Modified short-course radiotherapy
radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes: 25Gy/5Fx
Drug: PD-1 antibody
PD-1 antibody (Tislelizumab): 200mg d1 q3w
Drug: Capecitabine
Capecitabine: 1000mg/m2 d1-14 q3w
Drug: Oxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
|
Outcome Measures
Primary Outcome Measures
- Pathological complete response (pCR) rate [within 10 days after surgery]
The status of pCR will be evaluated after the TME surgery.
Secondary Outcome Measures
- Tumor regression grade [within 10 days after surgery]
TRG is evaluated according to the AJCC system. TRG0-1 is defined as good response, TRG2 as moderate response, and TRG3 as poor response.
- Local recurrence rate(LRR) [3 years after sugery]
Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology.
- Disease free survival(DFS) [3 years after surgery]
The three-year disease-free survival of patients.
- Overall survival(OS) [3 years after surgery]
The three-year overall survival of patients.
- Adverse effects rate [From date of initiation of treatment until the date of death from any cause, assessed up to 5 years]
Rate of radiotherapy, chemotherapy and immunotherapy related adverse events
- Rectal specific quality of life assessment via QLQ-CR29 [Baseline and months 3, 6, 12, 24, 36, 60 after the surgery]
Rectal specific quality of life according to European Organization for Research and Treatment of Cancer ( EORTC) Quality of life questionnaire QLQ-CR29. scale from 0 to 100, A higher scale represents better function and a higher quality of life.
- Quality of life assessment via QLQ-C30 [Baseline and months 3, 6, 12, 24, 36, 60 after the surgery]
Quality of life according to EORTC Quality of life Questionnaire QLQ-C30 version 3.0. Score range from 0 to 100 points. A higher score represents better function and a higher quality of life.
- Validation of the Wexner score [Months 3, 6, 12, 24, 36, 60 after the surgery]
The change of severity of fecal incontinence assessment according to Wexner score. a score from 0-20, where 0 is perfect continence and 20 is complete incontinence.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
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Male or Female aged 18-75.
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Patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic MRI and anorectoscopy, the clinical stage is cT2N+M0/cT3-4aN0/+M0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative, tumor occupies <2/3 circle of bowel lumen.
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Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive.
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Eastern Cooperative Oncology Group (ECOG) 0-1.
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No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation).
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Adequate hematologic, hepatic, renal, thyroid and cardiac function: white blood cells ≥3500/mm3, neutrophils ≥1800/mm3, platelets ≥100,000/mm3, hemoglobin ≥100 g/L; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × ULN; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN), bilirubin ≤1.25 × ULN, serum albumin ≥28 g/L. creatinine clearance ≥50 mL/mi, creatinine ≤1.5 × ULN;
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Informed consent form signed.
Exclusion Criteria:
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Patients with a previous history of malignant tumors besides rectal cancer.
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Patients with distant metastases before enrollment.
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Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT.
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Patients with obstruction, perforation, or bleeding that require emergency surgery.
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Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
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Allergic to any component of the therapy.
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Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma.
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Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
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Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
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Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities.
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Patients with congenital or acquired immune deficiency (such as HIV infection).
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Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.
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Other conditions that investigators consider not suitable for this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sir Run Run Shao hospital | Hanzhou | Zhejiang | China | 310012 |
Sponsors and Collaborators
- Sir Run Run Shaw Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SRRS-mRCAT