Node-sparing Radiotherapy Combined With Total Neoadjuvant CAPOX and Sintilimab for MSS Middle and Low Rectal Cancer

Official title

Total Neoadjuvant CAPOX And PD-1 Inhibitor（Sintilimab） Combined With Node-sparing Short-course Radiotherapy For MSS Locally Advanced Of Middle And Low Rectal Cancer(CASINOs): An Open Label, Single-arm, Prospective Clinical Trial

Overview

phase II clinical trial to evaluate node-sparing short-course radiation combined with total neoadjuvant CAPOX and Sintilimab for MSS locally advanced rectal cancers.

Detailed description

This is an open-label, prospective, single-center phase II clinical trial to evaluate node-sparing short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with total neoadjuvant CAPOX and PD-1 Inhibitor (Sintilimab) for patients with MSS locally advanced of middle and low rectal cancer. A total of 37 patients will be enrolled in this trial. The primary endpoint is the complete response(CR) rate, which includes cCR and pCR. The organ preservation rate, tumor regression grade, 3-year DFS, 3-year OS, and adverse effects will also be analyzed.

Interventions

• Radiation node-sparing short-course radiotherapy
  5Gy\*5d, radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes
• Drug Sintilimab
  200mg intravenous infusion d1 of each cycle\*6cycles
• Drug Capecitabine
  1000mg/m2, PO, BID, d1-14 of each cycle\*6cycles
• Drug Oxaliplatin
  130mg/m2, intravenous infusion,d1 of each cycle\*6cycles
• Procedure TME surgery
  laparoscopic or robotic TME surgery for non-cCR patients
• Procedure watch and wait
  WW for cCR patients

Primary outcome measures

• Complete response [Time frame: within 10 days after TNT therapy or surgery]

Secondary outcome measures (8)

• Tumor regression grade [Time frame: within 10 days after surgery]
• Local recurrence rate(LRR) [Time frame: 3 years after sugery]
• Disease free survival(DFS) [Time frame: 3 years after treatment]
• Overall survival(OS) [Time frame: 3 years after enrollment]
• Adverse effects rate [Time frame: From date of initiation of treatment until the date of death from any cause, assessed up to 5 years]
• Rectal specific quality of life assessment via QLQ-CR29 [Time frame: Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery]
• Quality of life assessment via QLQ-C30 [Time frame: Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery]
• Validation of the Wexner score [Time frame: Months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery]

Eligibility criteria

Inclusion criteria

• Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
• Male or Female aged 18-75.
• 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/cT3-4N0/+M0, the lymph nodes are limited to the mesorectum.
• 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.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation).
• 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;
• Informed consent form signed.

Exclusion criteria

• Patients with a previous history of malignant tumors besides rectal cancer.
• Patients with distant metastases before enrollment.
• Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT.
• Patients with obstruction, perforation, or bleeding that require emergency surgery.
• Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
• Allergic to any component of the therapy.
• Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma.
• Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
• Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
• 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.
• Patients with congenital or acquired immune deficiency (such as HIV infection).
• Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.

Other conditions that investigators consider not suitable for this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang University Affiliated Jinhua Hospital — Jinhua

Identifiers

NCT: NCT06204094 · Jinhua CH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗