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

Primary Purpose

Lynch Syndrome

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

PD-1 Antibody

About this trial

This is an interventional prevention trial for Lynch Syndrome focused on measuring Toripalimab, Lynch Syndrome, Prevention

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Sun Yat-sen University, Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Prevention group

Follow-up group

Arm Description

Toripalimab: 240mg IV every 3 months for a year

Routine follow-up, no intervention

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

The percentage of patients developing high-grade polyps on pathology within 5 years from randomization.

Treatment-related adverse events

Incidence and severity of adverse events as assessed by NCI CTCAE V4.0

Effectiveness with different genotypes or phenotypes

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

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

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

Full Information

NCT ID

NCT04711434

First Posted

January 13, 2021

Last Updated

January 18, 2021

Sponsor

Sun Yat-sen University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04711434

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2020 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lynch Syndrome

Keywords

Toripalimab, Lynch Syndrome, Prevention

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

260 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Prevention group

Arm Type

Experimental

Arm Description

Toripalimab: 240mg IV every 3 months for a year

Arm Title

Follow-up group

Arm Type

No Intervention

Arm Description

Routine follow-up, no intervention

Intervention Type

Drug

Intervention Name(s)

PD-1 Antibody

Other Intervention Name(s)

Toripalimab

Intervention Description

Toripalimab: 240mg IV every 3 months for a year

Primary Outcome Measure Information:

Title

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

Time Frame

up to 5 years

Secondary Outcome Measure Information:

Title

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

Time Frame

up to 5 years

Title

The percentage of patients developing high-grade polyps on pathology within 5 years from randomization.

Time Frame

up to 5 years

Title

Treatment-related adverse events

Description

Incidence and severity of adverse events as assessed by NCI CTCAE V4.0

Time Frame

up to 5 years

Title

Effectiveness with different genotypes or phenotypes

Description

Estimated the percentage of patients with different genotypes or phenotypes not developing polyps or second primary tumors within 5 years from randomization.

Time Frame

up to 5 years

Title

Disease-free Survival

Description

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

Time Frame

up to 5 years

Title

Overall Survival

Description

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

Time Frame

up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Peirong Ding, MD, Ph D

Phone

00862087343124

dingpr@sysucc.org.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Wu Jiang, MD, Ph D

Phone

00862087343920

jiangwu@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peirong Ding, MD, Ph D

Organizational Affiliation

Sun Yat-sen University

Official's Role

Study Chair

Facility Information:

Facility Name

Sun Yat-sen University, Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Peirong Ding, MD, Ph D

Phone

00862087343124

dingpr@sysucc.org.cn

12. IPD Sharing Statement

Learn more about this trial

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

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