Colorectal CarcinomaPhase 1NCT03300570
Dolcanatide in Preventing Colorectal Cancer in Healthy Volunteers
A Phase 1 study testing Dolcanatide, Laboratory Biomarker Analysis and Questionnaire Administration in people with Colorectal Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Carcinoma
- What is being tested?
- Dolcanatide, Laboratory Biomarker Analysis and Questionnaire Administration
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jul 2018to 17 May 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- PRE-REGISTRATION INCLUSION
- 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
- REGISTRATION INCLUSION
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- 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
Who cannot join
- PRE-REGISTRATION EXCLUSION
- 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 surgery involving the luminal gastrointestinal (GI) tract, including bariatric surgery; exception: prior appendectomy >= 60 days prior to pre-registration is not an exclusion criterion
- History of celiac disease
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- 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
- Use of anti-coagulants or anti-platelet agents within 5 days prior to anticipated sigmoidoscopy; exception: individuals taking aspirin will not be excluded and will not be subject to a wash-out period
- History of bleeding/coagulation problems
- Any medical condition reported by the participant or documented in the medical record that is judged by the investigator to constitute a risk to safe participation
- Known or suspected mechanical gastrointestinal obstruction
- REGISTRATION EXCLUSION
- Sigmoidoscopy finding requiring clinical intervention
- Use of any illicit or illegal substances detected by urinary drug screen
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
About this study
Official title: Phase I Double-Blind, Placebo-Controlled Trial of 27 mg Dolcanatide (SP-333) to Demonstrate Colorectal Bioactivity in Healthy Volunteers
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To identify the ability of dolcanatide (SP333), when administered as a single daily dose of 27 mg x 7 days, to induce a direct pharmacological effect on cGMP levels, based on biopsy samples from the rectum obtained pre- and post-intervention, as compared to placebo.
SECONDARY OBJECTIVES:
- To assess the pharmacodynamic (PD) response rate between arms (dolcanatide versus placebo).
II. To confirm the safety and tolerability of dolcanatide, as compared to placebo.
OUTLINE: Participants are randomized to 1 of 2 arms.
ARM A: Participants receive dolcanatide orally (PO) once daily (QD) for 7 days.
ARM B: Participants receive placebo PO QD for 7 days.
After completion of study, participants are followed up at 21 and 51 days.
- Conditions
- Colorectal Carcinoma
- Being tested
- Dolcanatide, Laboratory Biomarker Analysis, Placebo Administration, Questionnaire Administration
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolcanatideDrug
Also called SP 333, SP-333, SP333
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Placebo AdministrationOther
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (dolcanatide) | Experimental | Participants receive dolcanatide PO QD for 7 days. Receives: Drug: Dolcanatide; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration |
| Arm B (placebo) | Placebo comparator | Participants receive placebo PO QD for 7 days. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 7 days
Secondary outcomes (2)
Pharmacodynamic (PD) Response Rate
Each participant will be assessed for PD response. The calculation is based on the standardized difference in means for the pharmacological effect on cGMP levels at the participant level, where a subject with a z >= 1.645 will be considered a PD responder. A participant with a z < 1.645 will be considered a non-responder. The PD response rate (percentage) of patients are summarized below by arm.
Measured: 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
The overall adverse event rates (percentages) for grade 3 or higher adverse events regardless of attribution to treatment are reported below. The percentages below are summarized for Diarrhea.
Measured: Up to 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start27 Jul 2018
- Primary completion2 Jan 2019
- Study completion17 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David S Weinberg, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03300570
- Sponsor's protocol ID
- NCI-2017-01783
- Other IDs
- NCI-2017-01783, N01-CN-2012-00042, MAY2017-09-01, MAY2017-09-01, N01CN00042, P30CA015083
- Status last verified
- May 2021
- First submitted
- 2 Oct 2017
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Double-Blind, Placebo-Controlled Trial of 27 mg Dolcanatide (SP-333) to Demonstrate Colorectal Bioactivity in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03300570
- Acronym / sponsor ID
- NCI-2017-01783
- Conditions
- Colorectal Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 27 Jul 2018 (actual)
- Primary completion
- 2 Jan 2019 (actual)
- Study completion
- 17 May 2021 (actual)
- First posted
- 3 Oct 2017 (actual)
- Results
- Posted 17 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To identify the ability of dolcanatide (SP333), when administered as a single daily dose of 27 mg x 7 days, to induce a direct pharmacological effect on cGMP levels, based on biopsy samples from the rectum obtained pre- and post-intervention, as compared to placebo.
SECONDARY OBJECTIVES:
- To assess the pharmacodynamic (PD) response rate between arms (dolcanatide versus placebo).
II. To confirm the safety and tolerability of dolcanatide, as compared to placebo.
OUTLINE: Participants are randomized to 1 of 2 arms.
ARM A: Participants receive dolcanatide orally (PO) once daily (QD) for 7 days.
ARM B: Participants receive placebo PO QD for 7 days.
After completion of study, participants are followed up at 21 and 51 days.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (dolcanatide) | Experimental | Drug: Dolcanatide, Other: Laboratory Biomarker Analysis, Other: Questionnaire AdministrationParticipants receive dolcanatide PO QD for 7 days. |
| Arm B (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Placebo Administration, Other: Questionnaire AdministrationParticipants receive placebo PO QD for 7 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- PRE-REGISTRATION INCLUSION
- 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
Key exclusion criteria (24 listed)
- PRE-REGISTRATION EXCLUSION
- 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 surgery involving the luminal gastrointestinal (GI) tract, including bariatric surgery; exception: prior appendectomy >= 60 days prior to pre-registration is not an exclusion criterion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DolcanatideAlso: SP 333, SP-333, SP333Given PO | Drug | Arm A (dolcanatide) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm A (dolcanatide), Arm B (placebo) |
| Placebo AdministrationGiven PO | Other | Arm B (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Arm A (dolcanatide), Arm B (placebo) |
Primary outcome
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
Time frame: Baseline to 7 days
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.
2 secondary outcomes
Pharmacodynamic (PD) Response Rate
Time frame: 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
Time frame: Up to 21 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David S Weinberg principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dolcanatide, Laboratory Biomarker Analysis and Questionnaire Administration in people with Colorectal Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline to 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.