Trial of ERapa to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance

NCT04230499 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: EMT-FAP-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

Patients with Familial Adenomatous Polyposis (FAP) who are undergoing endoscopic surveillance will be given Encapsulated Rapamycin (eRapa) at one of three escalating doses/schedules for 12 months with the aim of reducing polyp burden.

Conditions

Familial Adenomatous Polyposis

Outcome Measures

Primary Outcomes (3)

• Frequency and severity of adverse events associated with low dose eRapa in FAP patients

  Safety and tolerability of eRapa as determined by graded toxicity assessed throughout the trial per CTCAE v5.0.

  All adverse events with start dates occurring any time after informed consent is obtained until 7 days (for non-serious adverse events) or 30 days (for serious adverse events) after the last day of study participation will be recorded.

• Determine the Recommended Phase 2 Dose (RP2D)

  The Recommended Phase 2 Dose (RP2D) will be determined by examining and analyzing safety/ adverse events as reflected by Outcome 1, dose delays, dose reductions, withdrawal of treatment secondary to low-grade toxicities, and serum pharmacokinetic monitoring.

  After informed consent is obtained up to 30 days after the last day of study participation.

• Efficacy of eRapa in delaying polyp progression in patients with FAP as measured by change in polyp burden over time.

  Percentage change from baseline in colorectal polyp burden as measure by endoscopy at 6 months.

  Time for each patient is baseline to 6 months.

Secondary Outcomes (5)

• Clinical effect of eRapa on polyp burden.

  Following patients out to 12 months.

• Clinical effect of eRapa on International Society for Gastrointestinal Hereditary Tumors Stage.

  Following patients out to 6 and 12 months.

• Clinical effect of eRapa on Spigelman Stage Score.

  Following patients out to 6 and 12 months.

• Clinical effect of eRapa on duodenal polyp number and burden.

  Following patients out to 6 and 12 months.

• Determine the effect of food on eRapa absorption

  2 months

Other Outcomes (1)

• Explore correlation between immune markers influenced by mTOR inhibition and clinical outcomes

  Following patients out to 12 months.

Study Arms (4)

Cohort 1

EXPERIMENTAL

Cohort 1 will receive 0.5mg of eRapa every other day.

Drug: Encapsulated Rapamycin (eRapa)

Cohort 2

EXPERIMENTAL

Cohort 2 will receive 0.5mg of eRapa daily with 7 days on therapy, followed by 7 days off therapy.

Drug: Encapsulated Rapamycin (eRapa)

Cohort 3

EXPERIMENTAL

Cohort 3 will receive 0.5 mg of eRapa daily.

Drug: Encapsulated Rapamycin (eRapa)

Food Effect

EXPERIMENTAL

Upon identification of the RP2D, after a 2 week washout (14 days), subjects will be randomized into a fed and fasted (2 weeks - 14 days) two period cross over, with an intervening 2 week washout (14 days) for a total of 2 months (8 weeks).

Drug: Encapsulated Rapamycin (eRapa)

Interventions

Encapsulated Rapamycin (eRapa) DRUG

eRapa is encapsulated rapamycin. The rapamycin is encapsulated in order to deliver the rapamycin at a consistent and lower dosage. eRapa is a capsule, and is administered orally.

Also known as: eRapa; Encapsulated sirolimus

Cohort 1; Cohort 2; Cohort 3; Food Effect

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign and date an informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, age at least 18 years at the time of consent.
• Phenotypic familial adenomatous polyposis (FAP) with disease involvement of the colorectum by either genetic or clinical diagnosis: Adenomatous polyposis coli (APC) germline mutation with or without family history, or with greater than a cumulative lifetime history of (\>) 100 adenomas in large intestine and a family history of FAP, or FAP phenotype post colectomy for polyposis with a family history of FAP. Minimum number of polyps required for enrollment is 10.
• Abilitiy to safely undergo endoscopy.
• Ability to take oral medication and be willing to adhere to the eRapa regimen.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of eRapa administration.
• A woman must agree not to breast feed or donate eggs (ova, oocytes) during the study and for a period of 12 weeks after the last administration of study drug.

You may not qualify if:

• Risk-reduction surgery (colectomy or partial colectomy) within the 12 months prior to screening.
• Use of non-steroidal anti-inflammatory drugs other than aspirin during the study. The use of 81 milligrams (mg) of aspirin a day or 650 mg of aspirin per week is allowed.
• Treatment with other FAP-directed drug therapy (including NSAID \[Non-steroidal anti-inflammatory drug\] drugs), unless completes a 4 week washout period prior to enrollment.
• Duodenum or colon/ rectum with high grade dysplasia or cancer on biopsy at screening.
• Duodenal or colorectal polyp \> 1 centimeter (cm) not excised at the screening evaluation.
• Pregnancy or breast feeding.
• Unable to provide consent or anticipated inability to attend appropriate follow-up visits.
• Serum creatinine or measured/ calculated creatinine clearance (or glomerular filtration rate \[GFR\]) \> 1.5 x ULN OR \< 30mL/min for participants with creatine levels \> 1.5 x institutional ULN. Bilirubin ≥ 1.5 x ULN unless conjugated bilirubin ≤ ULN; alkaline phosphatase \> 5 x ULN; ALT/AST \> 2 x ULN.
• INR or PT or aPTT \> 1.5 x institutional ULN unless the patient is receiving anticoagulant therapy as long as the PT or aPTT is within therapeutic range of intended use of anticoagulants.
• Proteinuria \> 1+ on urinalysis or \> 1g/24h on 24h urine.
• History of interstitial lung disease or non-infectious pneumonitis.
• Immunosuppressed state (e.g., HIV, use of chronic steroids), active, uncontrolled infection.
• On agents known to alter rapamycin metabolism significantly.
• Concurrent involvement in other clinical trials specifically evaluating chemoprevention in FAP.
• Patients with a colonic polyp burden too numerous to count.

Sponsors & Collaborators

• Rapamycin Holdings Inc.: lead
• Cancer Insight, LLC: collaborator
• Biodexa Pharmaceuticals: collaborator

Study Sites (4)

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

UT Health

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer. 2023 Oct;22(4):413-422. doi: 10.1007/s10689-023-00334-3. Epub 2023 Apr 29.

  PMID: 37119510 DERIVED

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• George E Peoples, MD

  Sponsor CMO

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will receive one of three doses in a dose-escalating fashion. Cohort 1 will receive 0.5mg every other day, Cohort 2 will receive 0.5mg daily with 7 days on therapy followed by 7 days off therapy, and Cohort 3 will receive 0.5 mg daily. Patients will serve as their own control; no placebo will be given. Additionally, a subset of participants will be included in a randomized, balanced, single-schedule, two-treatment period (fed versus fasted) crossover study. Participants will receive eRapa under fed or fasted conditions in the first period, and then crossover to the other treatment (fed to fasted and vice versa) following a 2 week washout. Under this design, participants serve as their own control and will allow the assessment of the effect of food on the anticipated R2PD of eRapa

Study Record Dates

• First Submitted: January 12, 2020
• First Posted: January 18, 2020
• Study Start: January 18, 2021
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: January 9, 2025

Record last verified: 2024-10

Locations

US (4)