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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Radiation: node-sparing short-course radiotherapy; Drug: Sintilimab; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: TME surgery; Procedure: watch and wait

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 47 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.

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: jinlin du, master; Phone Number: 86 13957998111; Email: djl9090@163.com
• Study Contact Backup: Name: cheng cai, master; Phone Number: 86 18395995912; Email: ColoSurg_cc@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Jinhua, Zhejiang, China, 0579
      • Zhejiang University Affiliated Jinhua Hospital
      • Contact: Cheng Cai, master; Phone Number: +8618395995912; Email: ColoSurg_cc@zju.edu.cn
      • Principal Investigator: Jinlin Du, master
      • Sub-Investigator: Cheng Cai, master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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/cT3-4aN0/+M0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Arm; Participants will receive 5*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: Radiation: node-sparing short-course radiation; Drug: PD-1 antibody (Sintilimab); Drug: Capecitabine; Drug: Oxaliplatin

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*8cycles; Other Names: IBI308; Drug: Capecitabine; 1000mg/m2, PO, BID, d1-14 of each cycle*8cycles; Drug: Oxaliplatin; 130mg/m2, intravenous infusion,d1 of each cycle*8cycles; Procedure: TME surgery; laparoscopic or robotic TME surgery for non-cCR patients; Other Names: total mesorectal excision; Procedure: watch and wait; WW for cCR patients; Other Names: WW

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response	Pathological complete response (pCR) ：absence of residual tumour on resected specimen. Clinical complete response（cCR）: no residual tumour visible on imaging or colonoscopy and biopsy.	within 10 days after TNT therapy or surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor regression grade	TRG is evaluated according to the AJCC system. TRG0-1 is defined as good response, TRG2 as moderate response, and TRG3 as poor response.	within 10 days after surgery
Local recurrence rate(LRR)	Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology.	3 years after sugery
Adverse effects rate	Rate of radiotherapy, chemotherapy and immunotherapy related adverse events	From date of initiation of treatment until the date of death from any cause, assessed up to 5 years
Disease free survival(DFS)	the time from randomization to recurrence of tumor or death	3 years after treatment
Overall survival(OS)	the time from randomization to death	3 years after enrollment
Rectal specific quality of life assessment via QLQ-CR29	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.	Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery
Quality of life assessment via QLQ-C30	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.	Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery
Validation of the Wexner score	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.	Months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery

Collaborators and Investigators

• Sponsor: Jinhua Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: neoadjuvant; immunotherapy; radiotherapy; rectal cancer; sintilimab; CAPOX; microsatellite stability; node-sparing
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: Jinhua CH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: JinhuaCH will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
• IPD Sharing Time Frame: inhuaCH will consider access to study data upon a written detailed request sent to JinhuaCH, from 6 months until 5 years after publication of summary data.
• IPD Sharing Access Criteria: The data shared will be limited to that required for independent mandated verification of the published results, the applicant will need authorization from JinhuaCH for personal access, and the data will only be transferred after signing of a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No