Healthy, no Evidence of DiseasePhase 1NCT01336387
Dose-Finding of Retinoid 9cUAB30 in Healthy Volunteers
A Phase 1 study testing retinoid 9cUAB30, pharmacological study and laboratory biomarker analysis in people with Healthy, no Evidence of Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase I trial studies the side effects and the best dose of retinoid 9cUAB30 in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of retinoid 9cUAB30 may keep cancer from forming. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, no Evidence of Disease
- What is being tested?
- retinoid 9cUAB30, pharmacological study and laboratory biomarker analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- ECOG performance status =< 1 (Karnofsky >= 70%)
- WBC >= 3000/mm^3
- Platelets >= 100,000mm^3
- Bilirubin =< upper limit of institutional normal
- AST =< upper limit of institutional normal
- Creatinine within institutional normal limits
Show all 36Show fewer
- Sodium =< upper limit of institutional normal
- Potassium =< upper limit of institutional normal
- Chloride =< upper limit of institutional normal
- Bicarbonate =< upper limit of institutional normal
- Fasting triglycerides =<1.5 x ULN
- Fasting cholesterol =< 1.5 x ULN
- Participants must agree to discontinue all vitamin supplements while taking study medication and for thirty days past the last dose of study medication
- The effects of 9cUAB30 on the developing human fetus are unknown; for this reason, women must agree to use TWO effective forms of birth control for the duration of study participation and for 30 days following the last dose of study medication
- The following persons are not considered to be able to father or bear children and therefore are eligible to participate without the use of concurrent birth control:
- Female with bilateral oophorectomy and/or hysterectomy
- Female with fallopian tubes cut, tied, or sealed
- Female with sterilization implant (e.g. Adiana, Essure) placed > 3 months prior to randomization
- Female post-menopausal (> 1 year since last menses)
- Male with vasectomy > 3 months prior to randomization
- One of the following methods of birth control must be used by women of childbearing potential:
- Combined oral contraceptive pill in continuous use for > 30 days prior to study entry
- Vaginal ring (e.g. NuvaRing) in continuous use for > 30 days prior to study entry
- Skin patch (e.g. Ortho Evra) in continuous use for > 30 days prior to study entry
- Injection (e.g. Depo-Provera, Noristerat®) in continuous use for > 30 days prior to study entry
- Copper IUD (e.g. ParaGard)
- Note: because of the decreased effectiveness of low dose progesterone-only contraceptive methods when used with retinoids, the following hormonal methods are NOT acceptable:
- Low dose progesterone only oral contraceptive pill ("mini pills" e.g. Micronor®, Nor-Q.D., Ovrette)
- Norplant subdermal implant
- Mirena® Hormonal Implanted Uterine Device (IUD)
- In addition to the above method of contraception, one of the following methods of contraception will ALSO be used for the duration of study participation and for 30 days following the last dose of study medication:
- Diaphragm, cervical cap, or cervical shield with spermicide
- Contraceptive sponge (e.g. Today Sponge)
- Condom (male or female type) plus spermicide
- Females of child-bearing potential must have a negative pregnancy test within the current menstrual cycle and within 7 days before starting drug
- Participants must have the ability to understand, and the willingness to sign, a written informed consent document
Who cannot join
- Participants may not be taking medications that might interact with 9cUAB30; detailed list of potentially interacting medications
- Participants may not be taking lipid lowering agents
- Participants may not be receiving any other investigational agents
- Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of retinoids
- Participants with an 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
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 9cUAB30, breastfeeding must be discontinued for the duration of study participation and for one month after the last dose of the study agent if the mother is treated with 9cUAB30
- Individuals known to be HIV-positive may not participate in this study; the uncertain immune status of HIV-positive people and the potential risks of taking part in this study are too great to justify this non-treatment therapy
- Individuals with a history of cancer diagnosis or reoccurrence < 5 years from study entry may not participate; however, individuals with a history of squamous or basal cell carcinoma of the skin < 5 years from study entry will not be excluded from this study; the effects of this study agent on the immune system of people at risk for recurring cancer are unknown
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
About this study
Official title: A Randomized, Double-Blind, Single-dose and Multi-dose Study of the Novel Retinoid, 9cUAB30, to Determine Pharmacokinetics and Safety
This randomized phase I trial studies the side effects and the best dose of retinoid 9cUAB30 in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of retinoid 9cUAB30 may keep cancer from forming.
Read the detailed description
PRIMARY OBJECTIVES:
- The primary objective is to determine the toxicities and recommended phase II dose of 9cUAB30. The co- primary objective is to characterize the urine and plasma single dose and steady state pharmacokinetics of 9cUAB30 in normal volunteers.
SECONDARY OBJECTIVES:
- To correlate the pharmacokinetics of 9cUAB30 with toxicity. II. To compare observed toxicity between placebo controls and each dose level. III. To assess for any change in single dose PK after repeat dosing (Day 1 vs. Day 36).
IV. To assess the following potential biomarkers of UAB30:
- Telomerase activity (measurement of telomeric repeats) in PBMCs.
- Gene expression of DNA methyltransferase in PBMCs.
- Gene expression of CYP2B6 in PBMCs.
OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.
ARM I: Participants receive retinoid 9cUAB30* orally (PO) on days 1-28.
ARM II: Participants receive placebo* PO on days 1-28.
Courses repeat every 28 days in the absence of unacceptable toxicity.
*NOTE: Participants receive doses on days 8, 15, 22 and 29 after they have fasted for 12 hours.
After completion of study treatment, patients are followed up on days 7 and 30.
- Conditions
- Healthy, no Evidence of Disease
- Being tested
- retinoid 9cUAB30, placebo, pharmacological study, laboratory biomarker analysis, cancer prevention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
retinoid 9cUAB30Drug
Given PO
placeboOther
Also called PLCB
Given PO
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
cancer preventionOther
Also called cancer prevention intervention
Disease prevention
| Study group | Role | What they receive |
|---|---|---|
| Arm I (retinoid 9cUAB30) | Experimental | Participants receive retinoid 9cUAB30* PO on days 1-28. Receives: Drug: retinoid 9cUAB30; Other: pharmacological study; Other: laboratory biomarker analysis; Other: cancer prevention |
| Arm II (placebo) | Placebo comparator | Participants receive placebo* PO on days 1-28. Receives: Other: placebo; Other: pharmacological study; Other: laboratory biomarker analysis; Other: cancer prevention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose of 9cUAB30 based on the MTD
Measured: 28 days
Pharmacokinetics of 9cUAB30 in normal volunteers
Using one-sample t-tests, or Wilcoxon signed-rank tests as appropriate in order to evaluate the single vs. steady state levels. An appropriate regression model will be used to explore the relationship of dose with change in PK.
Measured: Baseline, days 1, 8, 15, 22, 36, and 43
Secondary outcomes (2)
Correlation between pharmacokinetic and toxicity as assessed by CTCAE
Measured: Up to 36 days
Comparison of toxicity between placebo and controls as assessed by CTCAE
To compare toxicities at each dose level to placebo, the Chi-square test will be used for the presence or absence of toxicities, and Wilcoxon rank-sum tests will be used for CTCAE grade and investigator defined relationship data.
Measured: Up to 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2011 (estimated)
- Study startOct 2011
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy, no Evidence of DiseaseStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jill Kolesar, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01336387
- Sponsor's protocol ID
- NCI-2013-00468
- Other IDs
- CO10311, N01CN35153
- Status last verified
- May 2013
- First submitted
- 24 Mar 2011
- Last updated
- 9 Oct 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Single-dose and Multi-dose Study of the Novel Retinoid, 9cUAB30, to Determine Pharmacokinetics and Safety
- ClinicalTrials.gov ID
- NCT01336387
- Acronym / sponsor ID
- NCI-2013-00468
- Conditions
- Healthy, no Evidence of Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 50 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 15 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I trial studies the side effects and the best dose of retinoid 9cUAB30 in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of retinoid 9cUAB30 may keep cancer from forming.
Detailed description
PRIMARY OBJECTIVES:
- The primary objective is to determine the toxicities and recommended phase II dose of 9cUAB30. The co- primary objective is to characterize the urine and plasma single dose and steady state pharmacokinetics of 9cUAB30 in normal volunteers.
SECONDARY OBJECTIVES:
- To correlate the pharmacokinetics of 9cUAB30 with toxicity. II. To compare observed toxicity between placebo controls and each dose level. III. To assess for any change in single dose PK after repeat dosing (Day 1 vs. Day 36).
IV. To assess the following potential biomarkers of UAB30:
- Telomerase activity (measurement of telomeric repeats) in PBMCs.
- Gene expression of DNA methyltransferase in PBMCs.
- Gene expression of CYP2B6 in PBMCs.
OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.
ARM I: Participants receive retinoid 9cUAB30* orally (PO) on days 1-28.
ARM II: Participants receive placebo* PO on days 1-28.
Courses repeat every 28 days in the absence of unacceptable toxicity.
*NOTE: Participants receive doses on days 8, 15, 22 and 29 after they have fasted for 12 hours.
After completion of study treatment, patients are followed up on days 7 and 30.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (retinoid 9cUAB30) | Experimental | Drug: retinoid 9cUAB30, Other: pharmacological study, Other: laboratory biomarker analysis, Other: cancer preventionParticipants receive retinoid 9cUAB30* PO on days 1-28. |
| Arm II (placebo) | Placebo comparator | Other: placebo, Other: pharmacological study, Other: laboratory biomarker analysis, Other: cancer preventionParticipants receive placebo* PO on days 1-28. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- ECOG performance status =< 1 (Karnofsky >= 70%)
- WBC >= 3000/mm^3
- Platelets >= 100,000mm^3
- Bilirubin =< upper limit of institutional normal
- AST =< upper limit of institutional normal
Key exclusion criteria (8 listed)
- Participants may not be taking medications that might interact with 9cUAB30; detailed list of potentially interacting medications
- Participants may not be taking lipid lowering agents
- Participants may not be receiving any other investigational agents
- Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of retinoids
- Participants with an 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
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 |
|---|---|---|
| retinoid 9cUAB30Given PO | Drug | Arm I (retinoid 9cUAB30) |
| placeboAlso: PLCBGiven PO | Other | Arm II (placebo) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I (retinoid 9cUAB30), Arm II (placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (retinoid 9cUAB30), Arm II (placebo) |
| cancer preventionAlso: cancer prevention interventionDisease prevention | Other | Arm I (retinoid 9cUAB30), Arm II (placebo) |
Primary outcome
Recommended phase II dose of 9cUAB30 based on the MTD
Time frame: 28 days
Pharmacokinetics of 9cUAB30 in normal volunteers
Time frame: Baseline, days 1, 8, 15, 22, 36, and 43
Using one-sample t-tests, or Wilcoxon signed-rank tests as appropriate in order to evaluate the single vs. steady state levels. An appropriate regression model will be used to explore the relationship of dose with change in PK.
2 secondary outcomes
Correlation between pharmacokinetic and toxicity as assessed by CTCAE
Time frame: Up to 36 days
Comparison of toxicity between placebo and controls as assessed by CTCAE
Time frame: Up to 36 days
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2014.
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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.
Jill Kolesar principal investigator
University of Wisconsin, Madison
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 retinoid 9cUAB30, pharmacological study and laboratory biomarker analysis in people with Healthy, no Evidence of Disease, 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 36 inclusion and 8 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: stopped early, as of the sponsor's last update on 9 Oct 2014. 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?
The study was stopped early. Results are not available in the source record.
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?
Recommended phase II dose of 9cUAB30 based on the MTD (time frame: 28 days). The study lists 2 primary outcomes in all. 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 9 Oct 2014.