Clinical trial NCT04711434: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lynch Syndrome
Keywords: Toripalimab
Lynch Syndrome
Prevention
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Fujian Cancer Hospital
name: Guangdong Provincial People's Hospital
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: The Third Affiliated Hospital of Kunming Medical College.
First posted: 2021-01-15
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: The percentage of patients from randomization to the first appearance of one of the following: adenomatous polyps or second primary tumors
timeFrame: up to 5 years
Secondary outcomes:
measure: The percentage of patients developing polyps greater than 1cm within 5 years from randomization
timeFrame: up to 5 years
measure: The percentage of patients developing high-grade polyps on pathology within 5 years from randomization.
timeFrame: up to 5 years
measure: Treatment-related adverse events
timeFrame: up to 5 years
measure: Effectiveness with different genotypes or phenotypes
timeFrame: up to 5 years
measure: Disease-free Survival
timeFrame: up to 5 years
measure: Overall Survival
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University, Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Peirong Ding, MD, Ph D
role: STUDY_CHAIR
References: