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

NCT ID: NCT06204094

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-05
• Study Completion Date: 2028-09-01

Brief Summary

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 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.

Conditions

Locally Advanced Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

node-sparing short-course radiotherapy

Intervention Type: RADIATION

5Gy\*5d, radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes

Sintilimab

Intervention Type: DRUG

200mg intravenous infusion d1 of each cycle\*8cycles

Capecitabine

Intervention Type: DRUG

1000mg/m2, PO, BID, d1-14 of each cycle\*8cycles

Oxaliplatin

Intervention Type: DRUG

130mg/m2, intravenous infusion,d1 of each cycle\*8cycles

TME surgery

Intervention Type: PROCEDURE

laparoscopic or robotic TME surgery for non-cCR patients

watch and wait

Intervention Type: PROCEDURE

WW for cCR patients

Interventions

node-sparing short-course radiotherapy

5Gy\*5d, radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes

Intervention Type: RADIATION

Sintilimab

200mg intravenous infusion d1 of each cycle\*8cycles

Intervention Type: DRUG

Capecitabine

1000mg/m2, PO, BID, d1-14 of each cycle\*8cycles

Intervention Type: DRUG

Oxaliplatin

130mg/m2, intravenous infusion,d1 of each cycle\*8cycles

Intervention Type: DRUG

TME surgery

laparoscopic or robotic TME surgery for non-cCR patients

Intervention Type: PROCEDURE

watch and wait

WW for cCR patients

Intervention Type: PROCEDURE

Other Intervention Names

IBI308; total mesorectal excision; WW

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/cT3-4aN0/+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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinhua Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Cheng Cai

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhejiang University Affiliated Jinhua Hospital

Jinhua, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

jinlin du, master

Role: CONTACT

djl9090@163.com

86 13957998111

cheng cai, master

Role: CONTACT

ColoSurg_cc@zju.edu.cn

86 18395995912

Facility Contacts

Cheng Cai, master degree

Role: primary

ColoSurg_cc@zju.edu.cn

86+18395995912

Other Identifiers

Jinhua CH

Identifier Type: -

Identifier Source: org_study_id