PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients
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| ClinicalTrials.gov Identifier: NCT04711434 |
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Recruitment Status :
Recruiting
First Posted : January 15, 2021
Last Update Posted : January 20, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lynch Syndrome | Drug: PD-1 Antibody | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Estimated 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 : | November 1, 2020 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Prevention group
Toripalimab: 240mg IV every 3 months for a year
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Drug: PD-1 Antibody
Toripalimab: 240mg IV every 3 months for a year
Other Name: Toripalimab |
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No Intervention: Follow-up group
Routine follow-up, no intervention
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- 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 ]
- The percentage of patients developing polyps greater than 1cm within 5 years from randomization [ Time Frame: up to 5 years ]
- The percentage of patients developing high-grade polyps on pathology within 5 years from randomization. [ Time Frame: up to 5 years ]
- Treatment-related adverse events [ Time Frame: up to 5 years ]Incidence and severity of adverse events as assessed by NCI CTCAE V4.0
- Effectiveness with different genotypes or phenotypes [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04711434
| Contact: Peirong Ding, MD, Ph D | 00862087343124 | dingpr@sysucc.org.cn | |
| Contact: Wu Jiang, MD, Ph D | 00862087343920 | jiangwu@sysucc.org.cn |
| China, Guangdong | |
| Sun Yat-sen University, Cancer Center | Recruiting |
| Guangzhou, Guangdong, China, 510060 | |
| Contact: Peirong Ding, MD, Ph D 00862087343124 dingpr@sysucc.org.cn | |
| Study Chair: | Peirong Ding, MD, Ph D | Sun Yat-sen University |
| Responsible Party: | Pei-Rong Ding, Professor, Sun Yat-sen University |
| ClinicalTrials.gov Identifier: | NCT04711434 |
| Other Study ID Numbers: |
B2020-059-01 |
| First Posted: | January 15, 2021 Key Record Dates |
| Last Update Posted: | January 20, 2021 |
| Last Verified: | January 2021 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Toripalimab Lynch Syndrome Prevention |
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Colorectal Neoplasms, Hereditary Nonpolyposis Adenomatous Polyps Syndrome Disease Pathologic Processes Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Neoplastic Syndromes, Hereditary Digestive System Diseases |
Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Antibodies Immunologic Factors Physiological Effects of Drugs |