Dolcanatide in Preventing Colorectal Cancer in Healthy Volunteers

NCT03300570 | Completed Phase 1 Results DMC FDA Drug

• 5 other identifiers: NCI-2017-01783N01-CN-2012-00042MAY2017-09-01N01CN00042P30CA015083
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies how well dolcanatide works in preventing colorectal cancer in healthy participants. Dolcanatide is similar to a natural hormone released into the intestine. It is thought that people who have low levels of the hormone are more likely to get colon cancer. It may be possible to prevent colon cancer by giving a drug that is similar to the hormone, such as dolcanatide.

Conditions

Colorectal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pharmacological Effect on Cyclic Guanosine Monophosphate (cGMP) Levels for Dolcanatide Arm Versus (vs.) Placebo, as Measured by the Differences in Mean cGMP Levels After 7 Days of Intervention

  Pharmacological effect on cyclic guanosine monophosphate (cGMP) levels for dolcanatide arm versus (vs.) placebo, where this effect is defined as the arithmetic difference in mean cGMP levels before and after 7 days of dolcanatide from subject biopsies. This represents the increase in cGMP stimulated by 7 days of dolcanatide in an individual subject. The mean cGMP value will be calculated based on 6 biopsies collected from the rectum during a flexible sigmoidoscopy procedure. Each biopsy was analyzed in triplicate using a commercially available EIA kit.

  Baseline to 7 days

Secondary Outcomes (2)

• Pharmacodynamic (PD) Response Rate

  Baseline to 7 days

• Percentage of Participants With Grade 3 or Higher Diarrhea Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 21 days

Study Arms (2)

Arm A (dolcanatide)

EXPERIMENTAL

Participants receive dolcanatide PO QD for 7 days.

Drug: Dolcanatide; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

Arm B (placebo)

PLACEBO COMPARATOR

Participants receive placebo PO QD for 7 days.

Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Questionnaire Administration

Interventions

Dolcanatide DRUG

Given PO

Also known as: SP 333, SP-333, SP333

Arm A (dolcanatide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (dolcanatide); Arm B (placebo)

Placebo Administration OTHER

Given PO

Arm B (placebo)

Questionnaire Administration OTHER

Ancillary studies

Arm A (dolcanatide); Arm B (placebo)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and willingness to sign a written informed consent document and follow study procedures
• Willing to abstain from grapefruit juice during study
• Willing to employ adequate contraception for men and women of childbearing potential; Note: acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status documented by serum follicle stimulating hormone (FSH), and/or documentation of surgical sterilization
• Willing to provide blood and tissue specimens for research purposes
• Normal organ function and have normal laboratory findings without clinically significant findings
• Leukocytes \>= 3 x 10\^3/microliter (B/L)
• Absolute neutrophil count \>= 1.5 x 10\^3/microliter (B/L)
• Platelets \>= 100 x 10\^3/microliter (B/L)
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal (ULN)
• Creatinine =\< institutional upper limit of normal
• Body mass index \< 35 kg/m\^2
• No findings in the rectum of advanced adenoma, chronic inflammation, or cancer

You may not qualify if:

• Documented history of advanced adenomas (\>= 1 cm in maximal diameter, \>= 3 in total number, villous morphology, or high-grade dysplasia) or colorectal cancer
• Family history of polyposis syndrome (e.g., familial adenomatous polyposis \[FAP\], hereditary nonpolyposis colorectal cancer \[HNPCC\]) or colorectal cancer (first degree relatives younger than 60 years old)
• History of gastroparesis
• History of celiac disease
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• Previous diagnosis of irritable bowel syndrome, chronic constipation, functional bowel disorders, colonic motility disorder, or opioid-induced constipation
• Any malignancy within 3 years of baseline; exception: participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator
• Currently receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dolcanatide or to any of the excipients
• History of difficulty with sigmoidoscopy or abnormal colorectal anatomy
• Uncontrolled current 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 or lactating women
• Current use of laxatives more than 3 times per week
• Current use of \>= 5 cigarettes/day
• Current use of \>= 3 alcoholic drinks/day

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

dolcanatide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: David Weinberg, M.D., M.Sc.
• Organization: Fox Chase Cancer Center

david.weinberg@fccc.edu

215-214-1424

Study Officials

• David S Weinberg

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 3, 2017
• Study Start: July 27, 2018
• Primary Completion: January 2, 2019
• Study Completion: May 17, 2021
• Last Updated: June 14, 2021
• Results First Posted: December 17, 2019

Record last verified: 2021-05

Locations

US (1)