Clinical trial NCT06641310: Trial of Exercise Therapy in Familial Adenomatous Polyp (FAP)
Official title: Phase 1a/b Trial of Exercise Therapy in Familial Adenomatous Polyp (FAP)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Familial Adenomatous Polyposis
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-10-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The study intervention being investigated in this phase 1a/b trial is exercise therapy. The form of exercise therapy will be aerobic exercise therapy comprised of supervised moderate-intensity treadmill walking.

The primary objective of this study is to identify the most appropriate level (the recommended phase 2 dose; RP2D) of exercise therapy for investigation in larger trials. To identify the RP2D of exercise therapy we will conduct a phase 1a level-finding trial and a phase 1b level-expansion trial. The phase 1a study is a level escalation trial evaluating 3 exercise levels (150, 225, and 300 minutes per week), with one de-escalation level of 90 minutes per week, if required. The phase 1b trial will further evaluate the highest feasible level and one LEVEL below identified in the phase 1a study.


Eligibility criteria: Inclusion Criteria:

* Individuals with FAP as defined by:

  * Genetic diagnosis: APC germline mutation (with or without FAP family history), OR
  * Clinical diagnosis: FAP phenotype with a history of more than 50 colorectal adenomas
* Have an intact rectum defined as status post colectomy and ileocolonic anastomosis for polyposis or pre-colectomy
* ≥ 5 rectal polyps \> 2 mm in size on baseline lower endoscopy
* Participants must have no evidence of invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation)
* No initiation of daily use of sulindac, celecoxib or other non-steroidal anti-inflammatory medications (NSAIDs) within 3 months of day 1 and no initiation \> 25% of the time (\> 8 days/month) for the duration of study participation
* No initiation of semaglutide, liraglutide (glucagon-like peptide-1 receptor agonist \[GLP-1 receptor agonist\]), tirzepatide (glucose-dependent insulinotropic polypeptide \[GIP\]), orlistat (lipase inhibitor) or other weight loss medications, within 3 months of day 1 and during study participation
* Adults ≥ 18 years of age
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
* Lower endoscopy, required for participation in the study, is contraindicated in pregnancy. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and until after the end of study endoscopy is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform the study team immediately
* Inactive defined as ≤ 60 minutes of moderate or strenuous exercise per week over the past month as assessed by the Godin Leisure Time Exercise Questionnaire
* No self-reported contraindications to regular exercise as evaluated by the Physical Activity Readiness Questionnaire (PAR-Q+)
* Sufficient space to house a treadmill in primary residence for the intervention period or access to an approved treadmill (as determined by study exercise physiologist) for the intervention period (e.g., participant may have access to a treadmill via an existing membership to a health club)
* Ability for study team to deliver and install exercise equipment in primary residence

  * Note: If participant will be using treadmill from another source approved by study exercise physiologist, this inclusion criteria is not applicable
* Internet or Wi-Fi connection. For participants without internet or Wi-Fi, a pre-paid cellular iPad will be provided
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
* Physician approval
* Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

* History of total proctocolectomy
* Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening
* History of pelvic radiation
* Participants receiving any other investigational agents
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
* Pregnant women are excluded since endoscopy is not recommended while pregnant

Primary outcomes:
measure: Exercise therapy compliance (feasibility)
timeFrame: between 4-12 weeks
Secondary outcomes:
measure: Physiological changes
timeFrame: Baseline up to 26 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Samara Rifkin
role: PRINCIPAL_INVESTIGATOR
References: