Clinical trial NCT06507371: Node-sparing Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Rectal Cancer
Official title: Node-sparing Modified Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Locally Advanced of Middle and Low Rectal Cancer : An Randomized, Prospective, Multicenter, Open-label, Phase III Clinical Trial (mRCAT-III)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rectal Cancer
Keywords: node-sparing radiation
PD-1
MSS
short-course radioation
Lead sponsor: Sir Run Run Shaw Hospital
Sponsor class: OTHER
First posted: 2024-07-18
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, prospective, multicenter, open-label, Phase III clinical trial to evaluate node-sparing modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) compared with standard short-course radiation combined with CAPOX for patients with MSS middle and low rectal cancer. A total of 170 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The EFS rate, ORR, organ preservation rate, long-term prognosis, and adverse effects will also be analyzed.


Eligibility criteria: Inclusion Criteria:

1. Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
2. Male or Female aged 18-75.
3. 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 cT3-4bN0/+M0, and the lymph nodes are limited to the mesorectum.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) 0-1.
6. No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation).
7. 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;
8. Informed consent form signed.

Exclusion Criteria:

1. Patients with a previous history of malignant tumors besides rectal cancer.
2. Patients with distant metastases before enrollment.
3. Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT.
4. Patients with obstruction, perforation, or bleeding that require emergency surgery.
5. Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
6. Allergic to any component of the therapy.
7. Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma.
8. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
9. Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
10. 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.
11. Patients with congenital or acquired immune deficiency (such as HIV infection).
12. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.
13. Other conditions that investigators consider not suitable for this study.

Primary outcomes:
measure: pathological complete response (pCR) rate
timeFrame: within 10 days after completion of surgery
Secondary outcomes:
measure: event free survival (EFS)
timeFrame: 3 years after randomization
measure: overall response rate (ORR)
timeFrame: within 10 days after completion of chemotherapy
measure: organ preservation rate
timeFrame: within 10 days after completion of chemotherapy
measure: Disease free survival(DFS)
timeFrame: 3 years after chemotherapy or surgery
measure: Overall survival(OS）
timeFrame: 3 years after chemotherapy or surgery
measure: Adverse effects rate
timeFrame: From date of initiation of treatment until the date of death from any cause, assessed up to 5 years
measure: Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery
measure: Quality of life assessment via QLQ-C30
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery
measure: Validation of the Wexner score
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: Sir Run Run Shao hospital
state: Zhejiang
Study officials:
References: