Neoadjuvant Chemoradiotherapy Plus Tislelizumab Followed by TME for LARC.

February 7, 2022 updated by: Zhongtao Zhang, Beijing Friendship Hospital

Rationale and Design of a Prospective, Multicenter Phase Ⅱ Clinical Trial of Safety and Efficacy Evaluation of Long Course Neoadjuvant Chemoradiotherapy Plus Tislelizumab Followed by TME for LARC.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100050
        • Recruiting
        • Beijing Friendship Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Patients have been fully aware of the content of this study and signed the informed consent voluntarily;
  • Patients with rectal cancers must satisfied all the following conditions: Stage II/III LARC (cT1-3N1-2M0)；Tumor distal location ≤10 cm from anal verge (MRI diagnosed);
  • Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1;
  • Physical and viscera function of patients can withstand major abdominal surgery;
  • Patients are willing and able to follow the study protocol during the study;
  • Patients give consent to the use of blood and pathological specimens for study;
  • Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose.

Exclusion criteria:

  • Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time;
  • Patients underwent major surgery within 4 weeks prior to study treatment;
  • Patients have any condition affects the absorption of capecitabine through gastrointestinal tract;
  • Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
  • Patients who are allergic to any of the ingredients under study;
  • Patients with severe concomitant diseases with estimated survival ≤ 5 years;
  • Patients with present or previous moderate or severe liver and kidney damage presently or previously;
  • Patients have received other study medications or any immunotherapy currently or in the past;
  • Patients preparing for or previously received organ or bone marrow transplant;
  • Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy;
  • Patients with congenital or acquired immune deficiency (such as HIV infection);
  • If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance;
  • Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities.
  • Pregnant or lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Combination product: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pathologic complete response（pCR）
Time Frame: 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.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
neoadjuvant rectal (NAR) score
Time Frame: 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)
1 year
objective response rate (ORR)
Time Frame: 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)
1 year
R0 resection rate
Time Frame: 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.
1 year
anal preservation rate
Time Frame: 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.
1 year
3-year local recurrence rate (LRR)
Time Frame: 3 year
During the 3-year follow-up, the percentage of local recurrence.
3 year
3-year disease free survival (DFS)
Time Frame: 3 year
During the 3-year follow-up, the percentage of the patients who is disease free.
3 year
3-year overall survival (OS)
Time Frame: 3 year
During the 3-year follow-up, the percentage of the patients who is sill survival at the end of follow-up.
3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Friendship Hospital

Collaborators

Xuanwu Hospital, Beijing
Beijing Chao Yang Hospital
Tianjin Medical University General Hospital
Hangzhou New Horizon Health Technology Co., Ltd.
Beigene (Beijing) Biotechnology Co., Ltd
People's Hospital of Tianjin
Tianjin Medical University Cancer Institute & Hospital

Investigators

  • Study Chair: yaohongwei@ccmu.edu.cn Yao, Dr., Department of General Surgery, Beijing Friendship Hospital, Capital Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2021

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

May 23, 2021

First Submitted That Met QC Criteria

June 1, 2021

First Posted (Actual)

June 3, 2021

Study Record Updates

Last Update Posted (Actual)

February 23, 2022

Last Update Submitted That Met QC Criteria

February 7, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BFH-NCRTPD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Time Frame

2025.5-

IPD Sharing Access Criteria

via reasonable email requests

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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