A Biomarker Evaluation Trial of UAB30 in Renal Transplant Recipients at High Risk for Non-melanoma Skin Cancer

NCT03327064 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: UAB30
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled biomarker study in renal transplant recipients with actinic damage and a history of basal cell carcinomas and/or cutaneous squamous cell carcinomas. There will be two arms to the study: 1) daily oral UAB30 for 28 days; and 2) daily oral placebo for 28 days. The total duration of the study is anticipated to be 5 years. The hypothesis being tested is that a significantly greater percentage of subjects randomized to oral UAB30 over a period of 28 days will achieve ≥30% reduction in biomarkers of proliferation and ≥30% increase in apoptosis biomarkers than those who receive placebo. Cyclin D1 will serve as the primary biomarker. This investigation will determine whether subjects randomized to UAB30 have an increase in all trans-retinoic acid responsive genes in the skin compared to those receiving placebo. This will include an examination of target effects of UAB30 by evaluating its effects in vivo in humans on the DNA damage response and Src signaling pathways.

Conditions

Non-melanoma Skin Cancer

Outcome Measures

Primary Outcomes (1)

• Percent of subjects that achieve at least a 30% reduction in cyclin D1 expression in normal skin, in sun-exposed skin, and in actinic keratoses from baseline to the end of UAB30 administration (day 28)

  Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis at study initiation and again at day 28. The skin specimens will be processed for immunohistochemistry (IHC), which will be used for cyclin D1 expression. Quantification of cyclin D1 will be performed on microscopic sections by digital image analysis. Cyclin D1 will be measured at randomization (baseline) and after 28 days on UAB30.

  Baseline to day 28

Secondary Outcomes (23)

• Percent of subjects with 30% or greater decrease in proliferation as detected by Ki67 staining

  Baseline to day 28

• Percent of subjects with 30% or greater decreased proliferation as detected by PCNA staining

  Baseline (randomization) to day 28

• Percent of subjects with 30% or greater increased apoptosis as detected by the TUNEL assay

  Baseline (randomization) to day 28

• • Percent of subjects with 30% or greater decreased expression of the apoptotic protein Bcl-2

  Baseline (randomization) to day 28

• Percent of subjects with 30% or greater increased apoptosis as detected by cleaved caspase 3

  Baseline (randomization) to day 28

Study Arms (2)

Renal Transplant subjects receiving UAB30

ACTIVE COMPARATOR

Generally healthy renal transplant subjects receive UAB30 for 28 days with increased risk of non-melanoma skin cancer as evidenced by a history of prior squamous or basal cell skin cancer, ongoing or history of actinic keratoses and presence at baseline of at least 8 actinic keratosis on the face, neck, scalp and arms.

Drug: UAB30

Renal Transplant subjects receiving placebo

PLACEBO COMPARATOR

Generally healthy renal transplant subjects receive placebo for 28 days with increased risk of non-melanoma skin cancer as evidenced by a history of prior squamous or basal cell skin cancer, ongoing or history of actinic keratoses and presence at baseline of at least 8 actinic keratosis on the face, neck, scalp and arms.

Drug: Placebo

Interventions

UAB30 DRUG

9cUAB30 promotes homodimer and heterodimer formation with retinoic acid receptors (RARs), and was shown to inhibit breast tumor development in the N-methyl-N-nitrosourea (MNU)-induced rat mammary gland carcinoma model. The compound has also shown efficacy in rodent models of skin cancer. Dose administration will be 160mg daily for 28 days.

Renal Transplant subjects receiving UAB30

Placebo DRUG

This matches the UAB30 in appearance. Frequency of dosing will be daily for 28 days.

Renal Transplant subjects receiving placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Potential subjects will have at least 8 actinic keratoses (as determined by study dermatologists or qualified designee ).
• ECOG performance status of 0 or 1.
• Participants must have normal organ and marrow function as defined below:
• WBC ≥ 3000/mm3; platelets ≥ 100,000mm3, hemoglobin \>10 g/dL
• Bilirubin ≤ upper limit of institutional normal
• Creatinine within institutional normal limits
• Sodium, Potassium, Chloride, Bicarbonate: all ≤ upper limit of institutional normal
• Fasting Triglycerides ≤1.5xULN and Fasting Cholesterol ≤1.5x ULN
• Women of child-bearing potential and men must agree to use two effective forms of birth control prior to study entry and for the duration of study participation and for one month after study completion. Low dose progesterone only birth control pills are not an acceptable form of birth control due to lowered birth control efficacy with retinoids. Males who have had a vasectomy are not considered able to father a child, and therefore are eligible to participate without the use of concurrent birth control. Women who have had a bilateral oophorectomy, hysterectomy, or are greater than 1 year since their last menses, are not considered to be of child-bearing potential, and therefore are eligible to participate without the use of concurrent birth control.
• Each of the following is considered to be a single effective method of birth control:
• Combined oral contraceptive pill if used for \>30 days prior to entry into the study and continued for 30 days after the last dose of the study agent.
• Implanted hormone if in place for \>30 days prior to entry into the study and continued for 30 days after the last dose of the study agent.
• Any implanted device
• Vasectomy

You may not qualify if:

• Participants may not be taking medications which might interact with UAB30.
• 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.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with UAB30, 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 UAB30.
• 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 a study with low likelihood of benefit
• 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.
• Because of the uncertain risk of UAB30 to unborn fetuses and children, pregnant women and children will not be allowed in this study

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

UAB Dermatology

Birmingham, Alabama, 35233, United States

Location

Study Officials

• Craig Elmets, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 26, 2017
• First Posted: October 31, 2017
• Study Start: October 1, 2020
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)