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

Sun Yat-sen University

Status and phase

Enrolling

Phase 3

Conditions

Lynch Syndrome

Treatments

Drug: PD-1 Antibody

Study type

Interventional

Funder types

Other

Identifiers

NCT04711434

B2020-059-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

260 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Lynch syndrome with germline variants of MLH1, MSH2, or EPCAM (pathogenic or likely pathogenic variants)
Necessary treatments have been done, such as surgery, chemotherapy, radiation therapy, etc.
Have a resection, including right hemicolectomy, left hemicolectomy, sigmoid colectomy, or anterior resection of rectal cancer, or endoscopic adenoma resection
Aged 18-70 years old
Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
White blood cell (WBC) > 4000/mm3, Platelet count >100000/mm3, HB >10 g/dL
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
Serum creatinine (Scr) <1.8 mg/dL

Exclusion criteria

Lynch syndrome with germline variants of MSH6 and PMS2
Previous immunotherapy has been taken, such as anti-PD-1, anti-PD-L1, etc.
Long-term use of aspirin
Suffering from autoimmune diseases
Active infection with hepatitis B or hepatitis C (high copy number of viral DNA) or human immunodeficiency virus (HIV)
Other clinically serious active infections (NCI-CTC 4.0)
With cachexia or organ dysfunction
Suffering from seizures requiring treatment (such as steroids or antiepileptic therapy)
Unable to participate or complete the study due to substance abuse, or medical, psychological, or social disorder
Known allergy to any drugs in this study
Pregnant or nursing women, or women of childbearing potential who are not using adequate contraception
Any unstable condition or situation that could compromise the safety and compliance of participants.
Failure to sign an informed consent form