Overview

This trial is active, not recruiting.

Condition healthy subject
Treatments laboratory biomarker analysis, pharmacological study, placebo, retinoid 9cuab30
Phase phase 1
Sponsor National Cancer Institute (NCI)
Start date August 2013
End date December 2016
Trial size 40 participants
Trial identifier NCT01935960, N01CN35153, NCI-2013-01655, NCT01999127, P30CA014520, UW13022, UWI10-16-01R

Summary

This randomized phase I trial studies the side effects and best dose of retinoid 9cUAB30 in preventing cancer in healthy volunteers. The use of retinoid 9cUAB30 may keep cancer from forming in healthy volunteers.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Experimental)
Participants receive retinoid 9cUAB30 PO QD on days 1 and 8-36. Treatment continues in the absence of unacceptable toxicity.
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
retinoid 9cuab30 9cUAB30
Given PO
(Placebo Comparator)
Participants receive a placebo PO QD on days 1 and 8-36.
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
placebo placebo therapy
Given PO

Primary Outcomes

Measure
Recommended phase II dose of retinoid 9cUAB30, based on maximum tolerated dose (MTD), defined as the highest dose level with < 25% of treated patients experiencing a grade 2 toxicity or any treated patients experiencing a grade 3 or higher toxicity
time frame: Up to 30 days after completion of study treatment
Urine & plasma single dose & steady state PK of retinoid 9cUAB30, including maximum concentration (Cmax), time to peak concentration (Tmax), area under curve (AUC)0-least quantifiable concentration (lqc), AUC0-infinity, half-life (T½), and clearance (CL)
time frame: Baseline; 30, 45, 60, and 90 minutes; 2, 4, 6, 8, 12, 16, 20, and 24 hours on day 1; and 8, 15, 22, 29, 36, and 43 days

Secondary Outcomes

Measure
Change in single dose pharmacokinetics, including Cmax, Tmax, AUC0-lqc, AUC0-infinity, T1/2, and CL
time frame: Day 1 to day 36
Incidence of toxicity, graded according to the CTCAE version 4.0
time frame: Up to 30 days after completion of study treatment

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Normal volunteers, either male or female - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70% - White blood cell (WBC) >= 3000/mm^3 - Platelets >= 100,000/mm^3 - Hemoglobin > 10 g/dL - Bilirubin =< upper limit of institutional normal - Aspartate aminotransferase (AST) =< upper limit of institutional normal - Creatinine within institutional normal limits - Sodium, potassium, chloride, bicarbonate: all =< upper limit of institutional normal - Fasting triglycerides =< 1.5 x upper limit of normal (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 - Heterosexual women and men 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 - Men must agree not to donate sperm during the study and for three months after receiving the last dose of study drug - 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 intrauterine device (IUD) (e.g. ParaGard) - Note: 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 - Participants may not be taking lipid lowering agents - Participants may not receive any other investigational agents within 30 days of enrollment nor during study participation - 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 - 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 human immunodeficiency virus (HIV)-positive may not participate in this study - 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

Additional Information

Official title A Randomized, Double-Blind, Phase I Dose-Escalation Study of the Novel Retinoid 9cUAB30
Principal investigator Jill Kolesar
Description PRIMARY OBJECTIVES: I. To determine the toxicities and recommended phase II dose of 9cUAB30 (retinoid 9cUAB30). II. 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 pharmacokinetics (PK) after repeat dosing (day 1 vs. day 36). OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms. ARM I: Participants receive retinoid 9cUAB30 orally (PO) once daily (QD) on days 1 and 8-36. Treatment continues in the absence of unacceptable toxicity. ARM II: Participants receive a placebo PO QD on days 1 and 8-36. After completion of study treatment, patients are followed up at 7 and 30 days.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).