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

Locally Advanced Rectal Cancer Clinical Trial

— CASINOs  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06204094
• Other study ID #: Jinhua CH
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2024
• Est. completion date: September 1, 2028

Study information

• Verified date: January 2024
• Source: Jinhua Central Hospital
• Contact: jinlin du, master
• Phone: 86 13957998111
• Email: djl9090[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 37
• Est. completion date: September 1, 2028
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

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
• Capecitabine
1000mg/m2, PO, BID, d1-14 of each cycle*8cycles
• Oxaliplatin
130mg/m2, intravenous infusion,d1 of each cycle*8cycles

Procedure:
• TME surgery
laparoscopic or robotic TME surgery for non-cCR patients
• watch and wait
WW for cCR patients

Locations

Country	Name	City	State
China	Zhejiang University Affiliated Jinhua Hospital	Jinhua	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Jinhua Central Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Local recurrence rate(LRR)	Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology.	3 years after sugery
Secondary	Disease free survival(DFS)	the time from randomization to recurrence of tumor or death	3 years after treatment
Secondary	Overall survival(OS)	the time from randomization to death	3 years after enrollment
Secondary	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
Secondary	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
Secondary	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
Secondary	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