Trial Title:
Testing ONC201 to Prevent Colorectal Cancer
NCT ID:
NCT05630794
Condition:
Colorectal Adenomatous Polyp
Colorectal Carcinoma
Familial Adenomatous Polyposis
Multiple Adenomatous Polyps
Conditions: Official terms:
Colorectal Neoplasms
Adenomatous Polyposis Coli
Adenomatous Polyps
Polyps
TIC10 compound
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood
Arm group label:
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Colonoscopy
Description:
Undergo colonoscopy
Arm group label:
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Intervention type:
Drug
Intervention name:
Dordaviprone
Description:
Given PO
Arm group label:
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Other name:
Akt/ERK Inhibitor ONC201
Other name:
ONC201
Other name:
TIC10
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Complete questionnaire
Arm group label:
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Intervention type:
Procedure
Intervention name:
Sigmoidoscopy
Description:
Undergo sigmoidoscopy
Arm group label:
Prevention (ONC201, biopsy, sigmoidoscopy, colonoscopy)
Other name:
Proctosigmoidoscopy
Summary:
This phase I trial tests the safety, side effects, and best dose of Akt/ERK Inhibitor
ONC201 (ONC201) in preventing colorectal cancer in patients with familial adenomatous
polyposis (FAP) or a history of multiple polyps. ONC201 may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the optimal cancer preventive dose of ONC201 defined as the lowest dose
with less than or equal to 16.67% of participants experiencing unacceptable toxicity and
simultaneously resulting in a statistically significant increase in human adenoma tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL) expression.
SECONDARY OBJECTIVES:
I. To determine the lowest dose of ONC201 with less than or equal to 16.67% of
participants experiencing unacceptable toxicity and simultaneously resulting in a
statistically significant increase in normal human mucosa TRAIL expression.
II. To evaluate the safety and tolerability of multiple ascending doses of ONC201 when
administered weekly and every 3 weeks in participants with familial adenomatous polyposis
(FAP) or with multiple adenomas.
EXPLORATORY OBJECTIVES:
I. To evaluate the impact of ONC201 on:
Ia. Cytokine/immune response profiles (with attention to IL-10, IL-17A, TNF-alpha, IL-6,
granzyme A, and perforin) in sera, normal colonic mucosa, and adenomas; Ib. Serum TRAIL
concentration; Ic. Serum prolactin concentration; Id. Proliferation markers (Ki67), cell
death markers (BCL2, Caspase 3), stemness markers (LGR5, CD44, CD133, ALDH), and natural
killers (NK) cell infiltration in adenomas and in normal colonic mucosa; Ie. To evaluate
for associations between observed toxicity and TRAIL expression; If. To establish
organoids ex vivo and compare adenoma-derived organoid take rates between samples
obtained prior to and following treatment.
OUTLINE: This is a dose-escalation study.
Patients receive ONC201 orally (PO) once weekly (QW) or once every 3 weeks (Q3W) for 12
weeks. Patients also undergo collection of blood, tissue biopsy, and
sigmoidoscopy/colonoscopy throughout the study.
After completion of study treatment, patients are followed up for 4 weeks.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Be identified as high risk for recurrent colorectal adenomas, as defined by:
- A diagnosis of FAP AND/OR
- Findings of either > 5 small (less than 1 cm) adenomas OR >= 3 with at least
one >= 10 mm on most recent endoscopy performed in the past 5 years
- Be >= 18 years of age on day of signing informed consent
- Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky
>= 70%)
- Leukocytes >= 3,000/microliter
- Absolute neutrophil count >= 1,000/microliter
- Platelets >= 100,000/microliter
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase ([SGPT])
=< 1.5 x institutional upper limit of normal
- Creatinine =< 1.5 x institutional upper limit of normal
- Participant is due to undergo a standard of care lower gastrointestinal (GI)
colonoscopy for detection and removal of colorectal polyps. On this colonoscopy,
participant is required to have:
- Two (2) adenomatous polyps (pathologic confirmation of adenoma in non-FAP
participants is required prior to starting therapy) of at least five (5) mm in
size
- At least one (1) polyp within reach of a flexible sigmoidoscope (which will be
retained in the colon or rectum and marked)
- In addition to polypectomy, six (6) biopsies of normal colonic mucosa >= 1 cm
from a collected polyp will also be collected
- Willing to undergo a second, research intent endoscopic procedure (either
sigmoidoscopy or colonoscopy), approximately 12 weeks after initiating ONC201
treatment
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures
- Life expectancy of at least 5-years
- ONC201 is an imipridone agent with the potential for teratogenic or abortifacient
effects. For this reason and because imipridones potential teratogenic effects are
unknown, men and women of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry, for the duration of study participation, and for four weeks after study
treatment is completed. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should STOP the study medication and inform
her study physician immediately
- Ability to understand and the willingness to sign a written informed consent
document
Exclusion Criteria:
- Prior history of hereditary nonpolyposis colorectal cancer (HNPCC), also known as
Lynch syndrome
- Participants may not be currently receiving any other investigational agents or have
received any investigational agents within the past four weeks
- Prior history of invasive colorectal cancer
- Prior invasive active neoplasm that is progressing or requires active treatment
within 3 years from registration. Exceptions include basal cell carcinoma of the
skin or squamous cell carcinoma of the skin that has undergone potentially curative
therapy or in situ cervical cancer. Participants with a history of prior invasive
neoplasm diagnosed and treated greater than 3 years form registration may be
considered with consultation of the primary investigator
- Prior history of exposure to cytotoxic chemotherapy or ONC201
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to ONC201
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements
- Pregnant and women who are nursing are excluded from this study because ONC201 is an
imipridone agent with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events (AEs) in nursing
infants secondary to treatment of the mother with ONC201, breastfeeding should be
discontinued if the mother is treated with ONC201
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Michigan Comprehensive Cancer Center
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Contact:
Last name:
Elena M. Stoffel
Phone:
734-936-0781
Email:
estoffel@med.umich.edu
Investigator:
Last name:
Elena M. Stoffel
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Contact:
Last name:
Paul E. Wise
Phone:
314-454-7177
Email:
wisepe@wustl.edu
Investigator:
Last name:
Paul E. Wise
Email:
Principal Investigator
Facility:
Name:
Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Contact:
Last name:
Carol A. Burke
Phone:
216-444-6864
Email:
BURKEC1@ccf.org
Investigator:
Last name:
Carol A. Burke
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Contact:
Last name:
Peter P. Stanich
Phone:
614-293-6255
Email:
peter.stanich@osumc.edu
Investigator:
Last name:
Peter P. Stanich
Email:
Principal Investigator
Facility:
Name:
Rhode Island Hospital
Address:
City:
Providence
Zip:
02903
Country:
United States
Contact:
Last name:
Alexander G. Raufi
Phone:
401-787-0988
Email:
alexander_raufi@brown.edu
Investigator:
Last name:
Alexander G. Raufi
Email:
Principal Investigator
Start date:
October 8, 2024
Completion date:
January 1, 2028
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05630794
