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

• Status: Recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham

Criteria

Inclusion Criteria:

• ≥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

• Tubal ligation

• 2 barrier methods used together

• cervical cap + spermacide or foam

• diaphragm + spermacide or foam

• condom + spermacide or foam

• Females of child-bearing potential must have two negative urine pregnancy tests before starting drug; the first at the time of screening and a second pregnancy test within the first 5 days of their menstrual period.

• 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 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.

• Participants with an uncontrolled intercurrent illness including, but not limited to, ongoing, recurrent or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Depression is not exclusionary, but the investigator should make the determination if patients with depression are eligible.

• 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