Neoplasms

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Rare Diseases

Adenomatous Polyposis Coli

Colorectal Neoplasms

Nasopharyngeal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Polyps

Adenomatous Polyps

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Intestinal Polyposis

Genetic Diseases, Inborn

Familial Adenomatous Polyposis

MYH-associated Polyposis

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Amino Acids

Eflornithine

Sulindac

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Ornithine

Eflornithine \[250 mg tablet, three tablets (750 mg) orally once a day\]

Eflornithine placebo \[three tablets orally once a day\]

Eflornithine Placebo

Sulindac \[one tablet orally once a day\]

Sulindac 150 MG

Sulindac placebo \[one tablet orally once a day\]

Sulindac placebo

Carol Burke, M.D.

James Church, M.D.

Gabriella Möslein, M.D.

The purpose of this randomized, double-blind, Phase III trial is to determine if the combination of eflornithine plus sulindac is superior to sulindac or eflornithine as single agents in delaying time to the first occurrence of any FAP-related event. This includes: 1) FAP related disease progression indicating the need for excisional intervention involving the colon, rectum, pouch, duodenum and/or 2) clinically important events which includes progression to more advanced duodenal polyposis, cancer or death.

Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)

Phase III Trial of the Safety and Efficacy of Eflornithine Combined With Sulindac Compared to Eflornithine, Sulindac as Single Agents in Patients With Familial Adenomatous Polyposis

Progression of disease by evaluation of FAP-related events over the course of study treatment

Global assessment of change in upper GI polyp burden. These are binary outcomes derived from scores assigned by the investigator during each procedure, using a scale (-2, -1, 0, +1, +2) which corresponds, respectively, to the investigator's overall qualitative assessment of: much worse, worse, no change, improved, much improved. Summarizes the corresponding 6- and 12-month investigator change scores according to whether or not there was any positive improvement at either month 6 (compared to baseline) or at month 12 (compared to baseline or month 6), under the condition that there be no worsening at either timepoint.

Global assessment of change in lower GI polyp burden. These are binary outcomes derived from scores assigned by the investigator during each procedure, using a scale (-2, -1, 0, +1, +2) which corresponds, respectively, to the investigator's overall qualitative assessment of: much worse, worse, no change, improved, much improved. Summarizes the corresponding 6- and 12-month investigator change scores according to whether or not there was any positive improvement at either month 6 (compared to baseline) or at month 12 (compared to baseline or month 6), under the condition that there be no worsening at either timepoint.

Cancer Prevention Pharmaceuticals, Inc.

Eflornithine 750 mg and Sulindac 150 mg

Eflornithine: Eflornithine \[250 mg tablet, three tablets (750 mg) orally once a day\]

Sulindac 150 MG: Sulindac \[one tablet orally once a day\]

Eflornithine Plus Sulindac

Eflornithine 750 mg and Placebo

Eflornithine: Eflornithine \[250 mg tablet, three tablets (750 mg) orally once a day\]

Sulindac placebo: Sulindac placebo \[one tablet orally once a day\]

Eflornithine Plus Sulindac Placebo

Sulindac 150 mg and Placebo

Eflornithine Placebo: Eflornithine placebo \[three tablets orally once a day\]

Sulindac 150 MG: Sulindac \[one tablet orally once a day\]

Sulindac Plus Eflornithine Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

Netherlands

Belgium

United States

United Kingdom

Germany

Spain

Region of Enrollment

Michelle Boytim

Intent to treat population with all FAP-related events

Number with FAP-related events

Number with Lower GI FAP-related events

Intent to treat population with 171 subjects. Intent to treat population with lower GI anatomy (ower GI population) to evaluate lower GI FAP related events with 158 subjects.

Number of Subjects With Any FAP-related Event.

Improved

Not Improved

Improvement in Investigator Upper GI Assessment

Improvement in Investigator Lower GI Assessment

Overall Study

Adenocarcinoma

Stomach Neoplasms

Atrophy

Carcinogenesis

Gastritis, Atrophic

Metaplasia

Precancerous Conditions

Gastritis

Neoplastic Processes

Stomach Cancer

Eflornithine\*, 2 tablets, Oral, Daily for 18 months

Eflornithine placebo, 2 tablets, Oral, Daily for 18 months

Eflornithine placebo

Doug Morgan, MD

Keith Wilson, MD

A clinical study of the efficacy of oral alpha-difluoromethylornithine (eflornithine or DFMO) in male and female subjects ages 30-60 with gastric premalignant lesions in two high risk regions of Latin America.

Primary Objective

- The difference in cell DNA damage between patients treated with DFMO and patients treated with placebo at 6 months. The cell DNA damage is measured using the percent positive gastric epithelial cells assessed by IHC for gamma H2AX. The mean difference between the two groups at 6 months will be calculated, accounting for their baseline measurements.

Secondary Objectives

* The difference in cell DNA damage between patients treated with DFMO and patients treated with placebo for 18 months, and then followed for an additional 6 months. The cell DNA damage is measured using the percent positive gastric epithelial cells assessed by IHC for gamma H2AX. The mean difference between the two groups at 18 and 24 months will be calculated, accounting for their baseline measurements.
* The differences in the gastritis histopathology score between patients treated with DFMO and patients treated with placebo for a total of 18 months, and followed for an additional 6 months. The gastritis histopathology score is measured with a quantitative scale 0.0-6.0, for atrophy, intestinal metaplasia, and dysplasia. The mean differences between the two groups at 6, 18, and 24 months will be calculated using mixed models, accounting for their baseline measurements.
* Number of patients with quantitative toxicities. Toxicities will be assessed per CTCAE criteria, and each toxicity will be assigned an adverse event (AE) term according to CTCAE definitions (each AE term = unique representation of a specific event used for medical documentation and scientific analyses), and graded as defined by CTCAE (grade 1 = mild; grade 2 = moderate; grade 3 = severe or significant but not immediately life-threatening; grade 4 = life-threatening; grade 5 = death).
* To evaluate whether candidate single nucleotide polymorphisms (SNPs) relevant to eflornithine (DFMO) efficacy.

Chemoprevention of Gastric Carcinogenesis

Targeted Chemoprevention of Gastric Carcinogenesis in High Risk Populations

The cell DNA damage is measured using the percent positive gastric epithelial cells assessed by IHC for gamma H2AX.The mean difference between the two groups at 6 months will be calculated, accounting for their baseline measurements.

The cell DNA damage is measured using the percent positive gastric epithelial cells assessed by IHC for gamma H2AX. The mean difference between the two groups at 18 and 24 months will be calculated, accounting for their baseline measurements.

The gastritis histopathology score is measured with a quantitative scale 0.0-6.0, for atrophy, intestinal metaplasia, and dysplasia. The mean differences between the two groups at 6, 18, and 24 months will be calculated using mixed models, accounting for their baseline measurements.

Toxicities will be assessed per CTCAE criteria, and each toxicity will be assigned an adverse event (AE) term according to CTCAE definitions (each AE term = unique representation of a specific event used for medical documentation and scientific analyses), and graded as defined by CTCAE (grade 1 = mild; grade 2 = moderate; grade 3 = severe or significant but not immediately life-threatening; grade 4 = life-threatening; grade 5 = death).

National Cancer Institute (NCI)

Vanderbilt-Ingram Cancer Center

Director, Latin America sites, Vanderbilt Institute for Global Health

Eflornithine: Eflornithine\*, 2 tablets, Oral, Daily for 18 months

Eflornithine placebo: Eflornithine placebo, 2 tablets, Oral, Daily for 18 months

Age, Categorical

Puerto Rico

Honduras

Douglas Morgan

The Difference in Cell DNA Damage, Based on Percent Positive Cells, Between Patients Treated With DFMO and Patients Treated With Placebo at 6 Months.

The Difference in Cell DNA Damage Between Patients Treated With DFMO and Patients Treated With Placebo for 18 Months, and Then Followed for an Additional 6 Months.

The Differences in the Gastritis Histopathology Score Between Patients Treated With DFMO and Patients Treated With Placebo for a Total of 18 Months, and Followed for an Additional 6 Months.

Number of Patients With Quantitative Toxicities.

6 Months (Primary End Point)

18 Months (Secondary Endpoint)

24 Months (End of Study)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)	NCT01483144	Familial Adenom...	Eflornithine Eflornithine Pl... Sulindac 150 MG Sulindac placeb...	18 Years -	Cancer Prevention Pharmaceuticals, Inc.
Chemoprevention of Gastric Carcinogenesis	NCT02794428	Gastric Cancer Gastric Intesti...	Eflornithine Eflornithine pl...	30 Years - 69 Years	Vanderbilt-Ingram Cancer Center
Trial of Eflornithine Plus Sulindac in Patients With Familial Adenomatous Polyposis (FAP)	NCT01483144	Familial Adenom...	Eflornithine Eflornithine Pl... Sulindac 150 MG Sulindac placeb...	18 Years -	Cancer Prevention Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for eflornithine placebo