Neoadjuvant Chemoradiotherapy Plus Tislelizumab Followed by TME for LARC.

Phase 2

Recruiting

• Conditions: Colorectal Neoplasms
• Interventions: Combination Product: long course radiotherapy + capecitabine + PD-1 monoclonal antibody treatment combinations

• Registration Number: NCT04911517
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

Long course radiotherapy plus neoadjuvant chemotherapy followed by resection total mesorecta excision has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1(programmed death 1) humanized IgG4 (Immunoglomin G4) monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China.

The aim of This NCRT-PD-1-LARC trial is to evaluate the efficacy and safety of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorecta excision for LARC. This NCRT-PD-1-LARC trial will be a prospective, multicenter and phase Ⅱ clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorecta excision. It will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 10cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by total mesorecta excision 6-12 week after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-05-23
• Study Start: 2021-06-01
• Study First Submitted QC: 2021-06-01
• Study First Posted: 2021-06-03
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-07
• Last Update Posted: 2022-02-23
• Primary Completion: 2022-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
long course radiotherapy + capecitabine + PD-1 monoclonal antibody treatment combinations	long course radiotherapy + capecitabine + PD-1 monoclonal antibody treatment combinations	long course radiotherapy + capecitabine + PD-1 monoclonal antibody treatment combinations in patients with locally advanced rectal cancer

Primary Outcome Measures

Name	Time	Method
pathologic complete response（pCR）	1 year	All the enrolled patients will receive total mesorectal excision (TME) 7-9 weeks after the end of long course radiotherapy. The rectal specimens will be evaluated by the pathologists who are experienced on the rectal cancer diagnosis according to the 1997 Dworak grading system. The rectal cancer will be classified into 5 grades. Grade 0-3 will be considered as non-pCR while grade 4 represent pCR.

Secondary Outcome Measures

Name	Time	Method
3-year disease free survival (DFS)	3 year	During the 3-year follow-up, the percentage of the patients who is disease free.
objective response rate (ORR)	1 year	ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR rate is the sum of complete response (CR) and partial response (PR)
R0 resection rate	1 year	During the surgical process, the surgeon will evaluate the level of cancer resection. It will be classified as R0, R1, R2 resection. Therefore, we can calculate R0 resection rate.
neoadjuvant rectal (NAR) score	1 year	The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. The NAR score was calculated according to the following formula: NAR score = \[5pN - 3(cT - pT) + 12\]2∕9.61. (clinical tumor (cT) stage, pathologic tumor (pT) stage, pathologic nodal (pN) stage)
3-year local recurrence rate (LRR)	3 year	During the 3-year follow-up, the percentage of local recurrence.
anal preservation rate	1 year	the surgeon will decide whether the anal can be preserved on the basis of the rectal cancer and intraoperative situation. anal preservation rate is the percentage of patients who achieve anal preservation.
3-year overall survival (OS)	3 year	During the 3-year follow-up, the percentage of the patients who is sill survival at the end of follow-up.

Trial Locations

Locations (1)

Beijing Friendship Hospital; 🇨🇳 Beijing, Beijing, China