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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04711434

Collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University (Other), Fujian Cancer Hospital (Other), Guangdong Provincial People's Hospital (Other), Guangdong Provincial Hospital of Traditional Chinese Medicine (Other), The Third Affiliated Hospital of Kunming Medical College. (Other)

260

Enrollment

Location

Arms

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lynch Syndrome	Drug: PD-1 Antibody	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prevention group Toripalimab: 240mg IV every 3 months for a year	Drug: PD-1 Antibody Toripalimab: 240mg IV every 3 months for a year Other Names: Toripalimab
No Intervention: Follow-up group Routine follow-up, no intervention

Arm

Intervention/Treatment

Experimental: Prevention group

Toripalimab: 240mg IV every 3 months for a year

Drug: PD-1 Antibody

Toripalimab: 240mg IV every 3 months for a year

Other Names:

Toripalimab

No Intervention: Follow-up group

Routine follow-up, no intervention

Outcome Measures

Primary Outcome Measures

The percentage of patients from randomization to the first appearance of one of the following: adenomatous polyps or second primary tumors [up to 5 years]

Secondary Outcome Measures

The percentage of patients developing polyps greater than 1cm within 5 years from randomization [up to 5 years]
The percentage of patients developing high-grade polyps on pathology within 5 years from randomization. [up to 5 years]
Treatment-related adverse events [up to 5 years]
Incidence and severity of adverse events as assessed by NCI CTCAE V4.0
Effectiveness with different genotypes or phenotypes [up to 5 years]
Estimated the percentage of patients with different genotypes or phenotypes not developing polyps or second primary tumors within 5 years from randomization.
Disease-free Survival [up to 5 years]
defined as the time from randomization to the first appearance of one of the following: primary tumor recurrence, or death without cancer event; or censored at date of last follow-up
Overall Survival [up to 5 years]
defined as the time from randomization to death from any cause. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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