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Immunologic Factors

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

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

Cohort 3 will receive 0.5 mg of eRapa daily.

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.

Encapsulated Rapamycin (eRapa)

George E Peoples, MD

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.

Patients with FAP who are undergoing endoscopic surveillance will be given eRapa at one of three escalating doses/ schedules (0.5mg every other day, 0.5mg daily every other week, or 0.5mg daily) for 12 months with the aim of reducing polyp burden. Patients will serve as their own controls. Patients will be assessed with surveillance endoscopy at baseline, 6 months, and 12 months for change in polyp burden. Correlation between immune markers and clinical outcomes will be explored.

This is a Phase IIa trial which will enroll at approximately 6-8 sites within the United States that have specialty expertise in FAP treatment and surveillance. The trial is anticipated to last approximately 24 months for treatment and follow up.

The trial will enroll 30 patients with the genetic or clinical diagnosis of FAP. The clinical diagnosis includes individuals with 100 or more cumulative tubular adenomas throughout the colorectum. Patients must be undergoing surveillance for known FAP and can include those with intact colons as well as those who have undergone surgical therapy. For those patients who have undergone partial or total colectomy, they must have documented residual polyps in their rectum for which they are receiving active surveillance.

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.

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

Phase IIA Trial of Encapsulated Rapamycin (eRapa) to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance

Immunologic response will be measured and will include overall assessment of T cell phenotype and function.

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

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.

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

Percentage change from baseline in colorectal polyp burden at 12 months.

Change from baseline in International Society for Gastrointestinal Hereditary Tumors Stage at 6 and 12 months.

Change from baseline in Spigelman Stage Score at 6 and 12 months in patients with polyps at baseline on EGD. The Spigelman scoring system assigns points (0, 1, 2, or 3) based on number of adenomas, size (mm), histology, and dysplasia. The scoring ranges from 0 to 12 points. A higher score is a worse outcome.

Percentage change from baseline in the duodenal polyp number and burden at 6 and 12 months in patients with polyps at baseline on EGD.

Spots Global Cancer Trial Database for encapsulated rapamycin (erapa)