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

NCT ID: NCT04711434

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-01
• Study Completion Date: 2025-12-31

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.

Conditions

Lynch Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Prevention group

Toripalimab: 240mg IV every 3 months for a year

Group Type: EXPERIMENTAL

PD-1 Antibody

Intervention Type: DRUG

Toripalimab: 240mg IV every 3 months for a year

Follow-up group

Routine follow-up, no intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

PD-1 Antibody

Toripalimab: 240mg IV every 3 months for a year

Intervention Type: DRUG

Other Intervention Names

Toripalimab

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: collaborator

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Guangdong Provincial Hospital of Traditional Chinese Medicine

OTHER

Sponsor Role: collaborator

The Third Affiliated Hospital of Kunming Medical College.

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Pei-Rong Ding

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peirong Ding, MD, Ph D

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

Sun Yat-sen University, Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Peirong Ding, MD, Ph D

Role: CONTACT

dingpr@sysucc.org.cn

00862087343124

Wu Jiang, MD, Ph D

Role: CONTACT

jiangwu@sysucc.org.cn

00862087343920

Facility Contacts

Peirong Ding, MD, Ph D

Role: primary

dingpr@sysucc.org.cn

00862087343124

Other Identifiers

B2020-059-01

Identifier Type: -

Identifier Source: org_study_id