PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients

Related Clinical Trial
Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome Evaluation of ArTificial Intelligence System (Gi-Genius) for adenoMa dEtection in Lynch Syndrome. DNA Adductomics for Colorectal Cancer Investigation PD-1 Antibody Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer Faecal Microbiota Characterization in Lynch Syndrome (LS) Patients With or Without Colorectal Neoplasia Evaluating the Cologuard Test for Use in Lynch Syndrome PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome Identifying and Caring for Individuals With Inherited Cancer Syndrome Predictive Factor Study of the Occurrence of Endometrial Cancer in Patients With Lynch Syndrome Liquid Biopsy Evaluation and Repository Development at Princess Margaret Direct Information to At-risk Relatives Family History Study on Cancer Risk Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer Biomarkers in Samples From Patients With Endometrial Cancer Genetic Risk: Whether, When, and How to Tell Adolescents Familial Colorectal Cancer Registry in Hispanics Prostate Cancer Screening Among Men With High Risk Genetic Predisposition Collecting Information From Patients and Family Members With Hereditary Colorectal Cancer Syndromes or Who Are at High Risk of Developing Colorectal Cancer Identifying Patients With Hereditary and Familial Colorectal Cancer by Using an Online Risk Tool Pediatric Reporting of Adult-Onset Genomic Results Trial to Compare eConsent With Standard Consent Among Prospective Biobank Participants MSI in Circulatory DNA of Endometrial Cancer Telemedicine vs. Face-to-Face Cancer Genetic Counseling Educational CD-ROM Compared With Standard Informed Consent for Patients With Colorectal Cancer or a Family History of Colorectal Cancer Implementation of a New Strategy to Identify HNPCC Patients Energy Balance Interventions in Increasing Physical Activity in Breast Cancer Gene Positive Patients, Lynch Syndrome-Positive Patients, CLL Survivors or High-Risk Family Members Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes The GEOLynch Cohort Study Universal Endometrial Cancer DNA Sequencing for Detection of Lynch Syndrome and Personalized Care Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families Naproxen in Preventing DNA Mismatch Repair Deficient Colorectal Cancer in Patients With Lynch Syndrome Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE) NBI Versus Indigo Carmine During Colonoscopy in Lynch Syndrome I-Scan For Colon Polyp Detection In HNPCC Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes Psychosocial Aspects of Genetic Testing for Hereditary Nonpolyposis Colon Cancer Ohio Colorectal Cancer Prevention Initiative Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy Molecular Screening for Lynch Syndrome in Denmark Atorvastatin ± Aspirin in Lynch Syndrome Syndrome Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Colorectal Cancer Uncertain Genetic Test Results for Lynch Syndrome High Definition White-Light Colonoscopy vs. Chromoendoscopy for Surveillance of Lynch Syndrome. Linked Color Imaging Versus High-definition White Light Endoscopy for the Detection of Polyps in Patients With Lynch Syndrome (LCI-LYNCH) Hereditary Nonpolyposis Colorectal Cancer in Taiwan-Related Genetic Study and Clinical Applications Molecular Screening for Lynch Syndrome in Southern Denmark Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer Multi-Organ Screening Recommendations in Patients With Lynch Syndrome Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Patients Meeting Chinese Lynch Syndrome Criteria Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome Integrating Genetic Testing for Lynch Syndrome in a Managed Care Setting Registry for Women Who Are At Risk Or May Have Lynch Syndrome

Brief Title

PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients

Official Title

PD-1 Antibody for the Prevention of Adenomatous Polyps and Second Primary Tumors in Patients With Lynch Syndrome: An Open-label, Multicenter, Randomized Controlled Clinical Trial

Brief Summary

      This study aims to explore the role of PD-1 Antibody in preventing adenomatous polyps and
      second primary tumors in patients with Lynch Syndrome. There two arms, one is the
      experimental arm (PD-1 antibody prevention group) and the other is the control arm (routine
      follow-up group). For the experimental group, Tripleitriumab (PD-1 antibody) is given every 3
      months for a year.
    

Detailed Description

      Lynch syndrome (LS) is a hereditary cancer syndrome that causes the majority of hereditary
      CRC and approximately 3% of all CRC. LS significantly increases the risk for an individual to
      develop CRC during their lifetime. Individuals with LS also have an increased risk to develop
      extracolonic cancers, including endometrial, gastric, ovarian, upper urinary tract, small
      bowel, biliary tract, CNS, and certain types of skin cancer. Given the hereditary nature of
      this syndrome, preventing second primary tumors in patients with Lynch Syndrome after surgery
      to the primary site is very important.

      The purpose of this study is to prevent adenomatous polyps and second primary tumors using
      PD-1 antibody (Tripleitriumab) in patients with Lynch Syndrome.

      The primary outcome of this study is the incidence of intestinal adenomatous polyps and
      secondary primary tumors. The secondary outcomes are the incidence of colorectal adenomatous
      polyps greater than 1cm, incidence of high-grade colorectal polyps, treatment-related adverse
      events, disease-free Survival and overall Survival.

      There are two groups: the PD-1 antibody prevention group and the routine follow-up group. For
      the PD-1 antibody prevention group, participants will receive Toripalimab 240mg IV every 3
      months for a year. For the routine follow-up group, there is no drug intervention.

      This whole study will take 5 years: the first year for recruiting and the latter four years
      for follow-up.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

The percentage of patients from randomization to the first appearance of one of the following: adenomatous polyps or second primary tumors

Secondary Outcome

 The percentage of patients developing polyps greater than 1cm within 5 years from randomization

Condition

Lynch Syndrome

Intervention

PD-1 Antibody

Study Arms / Comparison Groups

 Prevention group
Description:  Toripalimab: 240mg IV every 3 months for a year

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

260

Start Date

November 1, 2020

Completion Date

December 31, 2025

Primary Completion Date

December 31, 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Lynch syndrome with germline variants of MLH1, MSH2, or EPCAM (pathogenic or likely
             pathogenic variants)

          2. Necessary treatments have been done, such as surgery, chemotherapy, radiation therapy,
             etc.

          3. Have a resection, including right hemicolectomy, left hemicolectomy, sigmoid
             colectomy, or anterior resection of rectal cancer, or endoscopic adenoma resection

          4. Aged 18-70 years old

          5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1

          6. White blood cell (WBC) > 4000/mm3, Platelet count >100000/mm3, HB >10 g/dL

          7. Serum glutamic-oxaloacetic transaminase (SGOT) < 1.5 × the upper limit of normal
             (ULN), Serum glutamic pyruvic transaminase (SGPT) < 1.5 × ULN prior to randomization,
             Total bilirubin (TBIL) < 1.5 mg/dL

          8. Serum creatinine (Scr) <1.8 mg/dL

        Exclusion Criteria:

          1. Lynch syndrome with germline variants of MSH6 and PMS2

          2. Previous immunotherapy has been taken, such as anti-PD-1, anti-PD-L1, etc.

          3. Long-term use of aspirin

          4. Suffering from autoimmune diseases

          5. Active infection with hepatitis B or hepatitis C (high copy number of viral DNA) or
             human immunodeficiency virus (HIV)

          6. Other clinically serious active infections (NCI-CTC 4.0)

          7. With cachexia or organ dysfunction

          8. Suffering from seizures requiring treatment (such as steroids or antiepileptic
             therapy)

          9. Unable to participate or complete the study due to substance abuse, or medical,
             psychological, or social disorder

         10. Known allergy to any drugs in this study

         11. Pregnant or nursing women, or women of childbearing potential who are not using
             adequate contraception

         12. Any unstable condition or situation that could compromise the safety and compliance of
             participants.

         13. Failure to sign an informed consent form
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Peirong Ding, MD, Ph D, 00862087343124, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT04711434

Organization ID

B2020-059-01


Responsible Party

Principal Investigator

Study Sponsor

Sun Yat-sen University

Collaborators

 Second Affiliated Hospital, School of Medicine, Zhejiang University

Study Sponsor

Peirong Ding, MD, Ph D, Study Chair, Sun Yat-sen University


Verification Date

January 2021