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Carcinoma

Adenoma

Colorectal Neoplasms

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Neoplasms by Histologic Type

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

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Gastrointestinal Diseases

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Antineoplastic Agents

All Drugs and Chemicals

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Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cola

Participants receive nivolumab intravenously IV over 60 minutes on day 1. Treatment repeats every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity.

Joanne Jeter, MD, MS

This phase II trial studies how well nivolumab works in preventing colon adenomas in participants with Lynch syndrome and a history of surgery to remove part of the colon. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To determine if maintenance therapy with nivolumab can decrease the incidence of colon adenomas in a population of patients with genetic predisposition to colorectal cancer and a history of hemicolectomy due to colon cancer or advanced colon adenoma.

SECONDARY OBJECTIVES:

I. To assess the safety of nivolumab maintenance therapy in this population. II. To obtain preliminary data on the short-term incidence of advanced colon adenomas (measuring greater than 10 mm or with high-grade dysplasia) and colon and non-colonic cancers in Lynch patients treated with maintenance nivolumab.

EXPLORATORY OBJECTIVES:

I. To determine biomarkers of immunologic activity associated with biologic activity of nivolumab in this population.

OUTLINE:

Participants receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 3 months for a total of 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 3 months, every 6 months for 1 year, then every 12 weeks thereafter.

Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy

A Phase II Study of PD-1 Inhibition for the Prevention of Colon Adenomas in Patients With Lynch Syndrome and a History of Partial Colectomy

The associated confidence intervals will be reported and used to determine if the incidence rate is significantly different from that reported among Lynch patients not receiving nivolumab, 0.33.

The associated confidence interval will be reported and used to determine if the incidence rate is significantly different from 0.22, the reported incidence of high-risk adenomas among Lynch syndrome patients not receiving nivolumab.

The incidence rates of colon cancers in Lynch patients treated with nivolumab will be estimated with corresponding confidence intervals.

The incidence rates of non-colonic cancers in Lynch patients treated with nivolumab will be estimated with corresponding confidence intervals.

National Cancer Institute (NCI)

Joanne Jeter

Principal Investigator

Rare Diseases

Adenocarcinoma

Lynch Syndrome II

Small Intestinal Adenocarcinoma

Video capsule endoscopy

Giulia Martina Cavestro, MD PhD

Marta Puzzono, MD

Background Lynch syndrome is caused by a pathogenic variant in one of the four Mismatch Repair genes (MMR): MLH1, MSH2/Epcam, MSH6, or PMS2. These pathogenic variants confer a higher risk of developing colorectal and other cancers, including small bowel cancer. The risk of developing a small bowel adenocarcinoma is about 100 times higher compared to individuals without Lynch syndrome, and the lifetime risk of small bowel cancer is estimated at 4,2%.

The diagnosis of a small bowel cancer depends on videocapsule endoscopy (VCE). This device is swalled so that it can record images of the small bowel, which are then stored on a wearable device for about 8 hours. The capsule is then expelled in the feces while the images are transferred to a computer to be analysed. To date, there is conflicting evidence on the efficacy of small bowel cancer screening with VCE

Rationale: this registry study will collect prospective data from patients with LS undergoing VCE

Aim: evaluate the incidence of neoplastic and pre-neoplastic lesions in patients with LS during a VCE-based small bowel cancer screening study

Design: this is a multicentric, observational study that analyzes data from diagnostic techniques already approved. Patients will not undergo diagnostic procedures beyond what would be recommended by clinical practice.

Background Lynch syndrome (LS) is caused by a pathogenic germline defect in one of the mismatch repair genes (MMR), namely MLH1, MSH2/Epcam, MSH6, or PMS2. Such pathogenic defects confer a higher risk of developing not only colorectal cancer but also small bowel cancer (SBC). Patients with LS have a lifetime risk of SMB of 4.2%, with a relative risk of \>100, compared to the general population. Moreover, patients with LS may develop SBC at a younger age, compared to SBC in individuals without LS.

The diagnostic standard for SBC is video capsule endoscopy (VCE). This consists in swallowing a pill with a camera inside. The VCE will record the images through the gastrointestinal tract and send them via Bluetooth to a wearable device for roughly 8 hours The capsule is then expelled with feces while the images are stored in a computer for later revision. Today, the data on the efficacy of a screening program for SBC in patients with LS is controversial.

Rationale This register study will collect prospective data on the VCEs done on patients with LS

Objective To estimate the incidence of neoplasia and preneoplastic lesions of the small bowel in patients with LS via VCE

Design Multicentric observational study with the use of approved diagnostic devices. It will not modify the current standard of care. The study design will not mandate obligatory studies of further procedures besides those that are clinically approved.

Population At least 10 subjects/year by each center (400 patients by study completion)

Controindications to VCE

* Stenosis, obstructions, fistulas (suspected or known)
* Cardiac defibrillators or cardiac pace-makers.
* Dysphagia
* Inability to provide written informed consent.
* Pregnancy (suspected or known).

Risks of VCE VCE retention is the most dreaded adverse events. The risk may vary between 1.5 and 21%.

Allergic reactions may be possible due to the use of sticky electrodes on the skin.

Study duration 10 years from January 2016.

Confounders To date, not known.

Data management All results will remain confidential. Clinical data may become available at scientific meetings or in published articles, but patient anonymity will always be maintained

Statistics The incidence of neoplastic and preneoplastic lesions of the subjects included in the study will be estimated. The sample size was established on the basis of feasibility (10 subjects enrolled each year for each center in 10 years = 400 patients in total). The expected incidence of small bowel injury is approximately 5%. With 400 subjects it is possible to estimate the incidence with an accuracy of 2% estimated with a 95% confidence interval.

Descriptive statistical variables (mean, standard deviation, median, etc.) will be evaluated on the collected data.

Any relationships between these variables will be evaluated using inferential statistics (t-test, chi-squared, logistic regression analysis, multivariate analysis, etc.). Any relationship with a p-value less than 0.05 will be considered significant.

Ethics The investigators declare that the study will be conducted in accordance with the ethical principles deriving from the Declaration of Helsinki and the current legislation on Observational Studies.

Informed consent. All subjects will be informed of the purpose of the study, of the confidentiality of the personal data, and of the fact that this data may be subject to review, for study-related reasons, by authorized person other than the physician.

It will be emphasized that participation is entirely voluntary and that the patient can refuse further participation in the protocol at any time without affecting the patient's subsequent care. Informed consent will be obtained for all subjects included in the study prior to their inclusion in the present study, in accordance with national and local regulations.

Videocapsule Endoscopy in Lynch Syndrome

Role of Videocapsule Endoscopy in Lynch Syndrome: a Multicenter Italian Registry Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy	NCT03631641	Colon Adenoma Colon Carcinoma Lynch Syndrome MLH1 Gene Mutat... MSH2 Gene Mutat...	Nivolumab	18 Years -	Ohio State University Comprehensive Cancer Center
Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy	NCT03631641	Colon Adenoma Colon Carcinoma Lynch Syndrome MLH1 Gene Mutat... MSH2 Gene Mutat...	Nivolumab	18 Years -	Ohio State University Comprehensive Cancer Center
Videocapsule Endoscopy in Lynch Syndrome	NCT05704010	Lynch Syndrome Lynch Syndrome ... Lynch Syndrome ... MLH1 Gene Mutat... MSH2 Gene Mutat... MSH6 Gene Mutat... PMS2 Gene Mutat... Small Bowel Ade...	Video capsule e...	18 Years -	San Raffaele University

Spots Global Cancer Trial Database for msh2 gene mutation