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Dose-Finding of Retinoid 9cUAB30 in Healthy Volunteers
A Randomized, Double-Blind, Single-dose and Multi-dose Study of the Novel Retinoid, 9cUAB30, to Determine Pharmacokinetics and Safety
Studie Overzicht
Toestand
Conditie
Gedetailleerde beschrijving
PRIMARY OBJECTIVES:
I. 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:
I. 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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Wisconsin
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Madison, Wisconsin, Verenigde Staten, 53792
- University of Wisconsin Hospital and Clinics
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Arm I (retinoid 9cUAB30)
Participants receive retinoid 9cUAB30* PO on days 1-28.
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Correlatieve studies
Correlatieve studies
Andere namen:
Given PO
Disease prevention
Andere namen:
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Placebo-vergelijker: Arm II (placebo)
Participants receive placebo* PO on days 1-28.
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Correlatieve studies
Correlatieve studies
Andere namen:
Gegeven PO
Andere namen:
Disease prevention
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Recommended phase II dose of 9cUAB30 based on the MTD
Tijdsspanne: 28 days
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28 days
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Pharmacokinetics of 9cUAB30 in normal volunteers
Tijdsspanne: Baseline, days 1, 8, 15, 22, 36, and 43
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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.
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Baseline, days 1, 8, 15, 22, 36, and 43
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Correlation between pharmacokinetic and toxicity as assessed by CTCAE
Tijdsspanne: Up to 36 days
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Up to 36 days
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Comparison of toxicity between placebo and controls as assessed by CTCAE
Tijdsspanne: Up to 36 days
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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.
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Up to 36 days
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Jill Kolesar, University of Wisconsin, Madison
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Andere studie-ID-nummers
- NCI-2013-00468
- N01CN35153 (Subsidie/contract van de Amerikaanse NIH)
- CO10311
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