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Dose-Finding of Retinoid 9cUAB30 in Healthy Volunteers

7 octobre 2014 mis à jour par: National Cancer Institute (NCI)

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.

Aperçu de l'étude

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

50

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Wisconsin
      • Madison, Wisconsin, États-Unis, 53792
        • University of Wisconsin Hospital and Clinics

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 65 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Tripler

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Arm I (retinoid 9cUAB30)
Participants receive retinoid 9cUAB30* PO on days 1-28.
Études corrélatives
Études corrélatives
Autres noms:
  • études pharmacologiques
Given PO
Disease prevention
Autres noms:
  • cancer prevention intervention
Comparateur placebo: Arm II (placebo)
Participants receive placebo* PO on days 1-28.
Études corrélatives
Études corrélatives
Autres noms:
  • études pharmacologiques
Bon de commande donné
Autres noms:
  • PLCB
Disease prevention
Autres noms:
  • cancer prevention intervention

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Recommended phase II dose of 9cUAB30 based on the MTD
Délai: 28 days
28 days
Pharmacokinetics of 9cUAB30 in normal volunteers
Délai: 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.
Baseline, days 1, 8, 15, 22, 36, and 43

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Correlation between pharmacokinetic and toxicity as assessed by CTCAE
Délai: Up to 36 days
Up to 36 days
Comparison of toxicity between placebo and controls as assessed by CTCAE
Délai: Up to 36 days
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.
Up to 36 days

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Jill Kolesar, University of Wisconsin, Madison

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 octobre 2011

Achèvement primaire (Réel)

1 septembre 2012

Achèvement de l'étude (Réel)

1 septembre 2012

Dates d'inscription aux études

Première soumission

24 mars 2011

Première soumission répondant aux critères de contrôle qualité

13 avril 2011

Première publication (Estimation)

15 avril 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

9 octobre 2014

Dernière mise à jour soumise répondant aux critères de contrôle qualité

7 octobre 2014

Dernière vérification

1 mai 2013

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • NCI-2013-00468
  • N01CN35153 (Subvention/contrat des NIH des États-Unis)
  • CO10311

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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