Non-melanoma Skin CancerPhase 1/2NCT03327064
A Biomarker Evaluation Trial of UAB30 in Renal Transplant Recipients at High Risk for Non-melanoma Skin Cancer
A Phase 1/2 study testing UAB30 in people with Non-melanoma Skin Cancer, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-melanoma Skin Cancer
- What is being tested?
- UAB30
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 31 Aug 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
Show all 22Show fewer
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Non-melanoma skin cancers (NMSCs), which include basal cell carcinomas (BCCs) and cutaneous squamous carcinomas (SCCs), are the most common malignancy in the U.S.; it is estimated that >3.5 million new NMSCs this year. This represents a tremendous economic impact on the U.S. healthcare system. Most NMSC are caused by overexposure to ultraviolet radiation, and current methods for their prevention consist of recommendations for limitations to sun exposure and avoidance of indoor tanning beds, the regular application of sunscreens, and a variety of other photoprotective activities. Despite these measures, the incidence of NMSCs continues to rise.
NMSCs are a particular problem for organ transplant recipients (OTRs), who must take medicines to protect against rejection of their transplanted organ. These drugs suppress the host immune response that serves to identify and eliminate mutant and neoplastic keratinocytes before they can progress to clinically apparent cancers. Recent research indicates that these drugs also augment signal transduction pathways involved in skin tumor development. NMSCs develop much more frequently in long-term recipients of renal allografts and once present, they behave more aggressively. In immunosuppressed patients, the risk of developing SCCs is 65250-fold higher than in the general population, and the risk of BCCs is 10-fold greater. The rate of SCC metastases in organ transplant recipients is 7%, which is much higher than the general population. For this reason, there has been great interest in identifying novel agents for chemoprevention, which are suitable for use by OTRs.
There will be two groups to the study. Individuals, aged 18 years or older, who have had a renal transplant but are in otherwise general good health, will be given UAB30 (160 mg/day) and will be compared to individuals, aged 18 years or older, who have had a renal transplant and are in otherwise general good health who are given placebo. All participants must be at 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 the presence, at baseline, of at least eight actinic keratoses on the face, neck, scalp and arms. Subjects will be randomized to 28 days of:
- UAB30 at 160 mg/day, renal transplant recipients
- placebo renal transplant recipients
At baseline screening, informed consent will be obtained and skin will be examined for potential non-melanoma skin cancers. Any lesions that are clinically suspicious for non-melanoma skin cancer will be removed per standard of care prior to administration of drug. Actinic keratoses will not be removed during the 28 day study period. Two weeks later, once any lesions clinically suspicious for non-melanoma skin cancer have been removed, renal transplant recipients will be randomized to one of the treatment arms described above. Participants will return at 28 days and 112 days for assessment.
- At randomization and 28 days, 6mm punch biopsies, or the equivalent deep shave biopsies, will be taken for individual biomarkers from non-sun exposed skin, chronically sun exposed skin, and a pre-identified AK. The chronically sun-exposed skin to be biopsied will be no less than 1 cm from the AK to be biopsied.
- At baseline, at 28 days and at the end of study AK lesions will be assessed and counted, employing techniques that have been validated in other studies.
- All lesions suspicious for skin cancer will be biopsied and treated appropriately (per standard of care) throughout the study.
- Adverse events will be assessed, including NMSC and melanoma, from signing of the informed consent through the end of the trial.
- Conditions
- Non-melanoma Skin Cancer
- Being tested
- UAB30, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UAB30Drug
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.
PlaceboDrug
This matches the UAB30 in appearance. Frequency of dosing will be daily for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to day 28
Secondary outcomes (23)
Percent of subjects with 30% or greater decrease in proliferation as detected by Ki67 staining
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 Ki67 expression. Quantification of Ki67will be performed on microscopic sections by digital image analysis. Ki67 will be measured at randomization and after 28 days on UAB30.
Measured: Baseline to day 28
Percent of subjects with 30% or greater decreased proliferation as detected by PCNA staining
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 PCNA expression as a marker for cellular proliferation. Quantification of PCNA will be performed on microscopic sections by digital image analysis. PCNA will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased apoptosis as detected by the TUNEL assay
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 TUNEL assay done by using an in situ cell death detection, fluorescein kit. Quantification of TUNEL positive cells will be performed on microscopic sections by digital image analysis. TUNEL positive cells will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
• Percent of subjects with 30% or greater decreased expression of the apoptotic protein Bcl-2
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Protein will be isolated from skin biopsies and the biomarker will be assessed by Western blot analysis. Bcl-2 expression will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased apoptosis as detected by cleaved caspase 3
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Protein will be isolated from skin biopsies and the biomarker will be assessed by Western blot analysis. Cleaved caspase 3 expression will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increase in DNA damage repair as detected by a reduction in γH2AX staining
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Immunofluorescence will be used to assess γH2AX expression. Quantification of γH2AX positive cells will be performed on microscopic sections by digital image analysis at randomization and after 28 days on UAB30.
Measured: Baseline (randomization)to day 28
Percent of subjects with 30% or greater increased apoptosis as detected by DNA damage repair pathway proteins : p-γH2AX
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarkers will be assessed by qPCR. RNA for these biomarkers will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization)to day 28
Percent of subjects with 30% or greater increased expression of the phosphorylated form of the DNA repair protein ATM
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Protein will be isolated from skin biopsies and the biomarker will be assessed by Western blot analysis. Phosphorylated ATM will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein ATM.
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Proteins will be isolated from skin biopsies and the biomarkers will be assessed by Western blot analysis. The phosphorylated proteins will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein RAD51.
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Proteins will be isolated from skin biopsies and the biomarkers will be assessed by Western blot analysis. The phosphorylated proteins will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein ATR.
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Proteins will be isolated from skin biopsies and the biomarkers will be assessed by Western blot analysis. The phosphorylated proteins will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein CHK1/2.
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Proteins will be isolated from skin biopsies and the biomarkers will be assessed by Western blot analysis. The phosphorylated proteins will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response proteins ATR.
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. Proteins will be isolated from skin biopsies and the biomarkers will be assessed by Western blot analysis. The phosphorylated proteins will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater decreased numbers of CD4+ T-cellscount
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. The skin specimens will be processed for immunofluorescence, which will be used for CD4+ expression as a marker for immunological parameters. Quantification of CD4+ expression will be performed on microscopic sections by digital image analysis. CD4+ expression will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased numbers of CD8+ T-cells
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. The skin specimens will be processed for immunofluorescence, which will be used for CD8+ expression as a marker for immunological parameters. Quantification of CD8+ expression will be performed on microscopic sections by digital image analysis. CD8+ expression will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater change in all trans-retinoic acid target genes : (ATRA) responsive genes (DHRS3, STRA6, MUC21, GABRP, DHRS9)
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarker will be assessed by qPCR. RNA for these biomarkers will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater decreased expression of the immunological marker for regulatory T-cells, FoxP3
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarker will be assessed by qPCR. RNA for this biomarkers will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased expression of the immunological marker for regulatory T-cells: IFN-γ
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarkers will be assessed by qPCR. RNA for these biomarkers will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased expression of the immunological marker for regulatory T-cells: IL-10
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarker will be assessed by qPCR. RNA for these biomarkers will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased expression of the immunological marker for Th17 cells.
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarkers will be assessed by qPCR. RNA for these biomarkers will be measured at randomization and after 28 days on UAB30.
Measured: Baseline (randomization) to day 28
Percent of subjects with 30% or greater decreased proliferation as detected by genes associated with immunological parameters: IL-22
Skin biopsies will be performed on normal skin, sun-exposed skin and one actinic keratosis. RNA will be isolated from skin biopsies and the biomarkers will be assessed by qPCR. RNA for these biomarkers will be measured at randomization and after 28 days on UAB30
Measured: Baseline (randomization) to day 28
Number of subjects in each group with actinic keratosis at the end of treatment with UAB30 (day 28) and 84 days after the end of treatment with UAB30 (day 112).
AKs will be counted and recorded at randomization, after 28 days on UAB30 and 84 days later (day 112). At the end of the study, new, persistent and regressed AKs will be recorded. Total number of AKs, number of new AKs, and number of regressed AKs will be assessed.
Measured: Baseline (randomization) to day 112
Mean number of toxicities experienced by subjects in each group treatment with UAB30 without signs of significant toxicity in organ transplant recipients..
For all subjects the mean number of toxicities (grade 3 or 4) per subject will be reported.
Measured: baseline to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2017
- Study start1 Oct 2020
- Primary completion31 Aug 2023
- Study completion31 Aug 2023
Why it stopped: COVID-19 pandemic, unable to enroll participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-melanoma Skin CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Craig Elmets, University of Alabama at Birmingham
- Investigators
- Craig Elmets, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03327064
- Sponsor's protocol ID
- UAB30
- Status last verified
- Aug 2024
- First submitted
- 26 Oct 2017
- Last updated
- 7 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Biomarker Evaluation Trial of UAB30 in Renal Transplant Recipients at High Risk for Non-melanoma Skin Cancer
- ClinicalTrials.gov ID
- NCT03327064
- Acronym / sponsor ID
- UAB30
- Conditions
- Non-melanoma Skin Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: COVID-19 pandemic, unable to enroll participants
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 31 Aug 2023 (actual)
- First posted
- 31 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Non-melanoma skin cancers (NMSCs), which include basal cell carcinomas (BCCs) and cutaneous squamous carcinomas (SCCs), are the most common malignancy in the U.S.; it is estimated that >3.5 million new NMSCs this year. This represents a tremendous economic impact on the U.S. healthcare system. Most NMSC are caused by overexposure to ultraviolet radiation, and current methods for their prevention consist of recommendations for limitations to sun exposure and avoidance of indoor tanning beds, the regular application of sunscreens, and a variety of other photoprotective activities. Despite these measures, the incidence of NMSCs continues to rise.
NMSCs are a particular problem for organ transplant recipients (OTRs), who must take medicines to protect against rejection of their transplanted organ. These drugs suppress the host immune response that serves to identify and eliminate mutant and neoplastic keratinocytes before they can progress to clinically apparent cancers. Recent research indicates that these drugs also augment signal transduction pathways involved in skin tumor development. NMSCs develop much more frequently in long-term recipients of renal allografts and once present, they behave more aggressively. In immunosuppressed patients, the risk of developing SCCs is 65250-fold higher than in the general population, and the risk of BCCs is 10-fold greater. The rate of SCC metastases in organ transplant recipients is 7%, which is much higher than the general population. For this reason, there has been great interest in identifying novel agents for chemoprevention, which are suitable for use by OTRs.
There will be two groups to the study. Individuals, aged 18 years or older, who have had a renal transplant but are in otherwise general good health, will be given UAB30 (160 mg/day) and will be compared to individuals, aged 18 years or older, who have had a renal transplant and are in otherwise general good health who are given placebo. All participants must be at 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 the presence, at baseline, of at least eight actinic keratoses on the face, neck, scalp and arms. Subjects will be randomized to 28 days of:
- UAB30 at 160 mg/day, renal transplant recipients
- placebo renal transplant recipients
At baseline screening, informed consent will be obtained and skin will be examined for potential non-melanoma skin cancers. Any lesions that are clinically suspicious for non-melanoma skin cancer will be removed per standard of care prior to administration of drug. Actinic keratoses will not be removed during the 28 day study period. Two weeks later, once any lesions clinically suspicious for non-melanoma skin cancer have been removed, renal transplant recipients will be randomized to one of the treatment arms described above. Participants will return at 28 days and 112 days for assessment.
- At randomization and 28 days, 6mm punch biopsies, or the equivalent deep shave biopsies, will be taken for individual biomarkers from non-sun exposed skin, chronically sun exposed skin, and a pre-identified AK. The chronically sun-exposed skin to be biopsied will be no less than 1 cm from the AK to be biopsied.
- At baseline, at 28 days and at the end of study AK lesions will be assessed and counted, employing techniques that have been validated in other studies.
- All lesions suspicious for skin cancer will be biopsied and treated appropriately (per standard of care) throughout the study.
- Adverse events will be assessed, including NMSC and melanoma, from signing of the informed consent through the end of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Renal Transplant subjects receiving UAB30 | Active comparator | Drug: UAB30Generally 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. |
| Renal Transplant subjects receiving placebo | Placebo comparator | Drug: PlaceboGenerally 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- ≥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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UAB309cUAB30 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. | Drug | Renal Transplant subjects receiving UAB30 |
| PlaceboThis matches the UAB30 in appearance. Frequency of dosing will be daily for 28 days. | Drug | Renal Transplant subjects receiving placebo |
Primary outcome
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)
Time frame: Baseline to 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.
23 secondary outcomes
Percent of subjects with 30% or greater decrease in proliferation as detected by Ki67 staining
Time frame: Baseline to day 28
Percent of subjects with 30% or greater decreased proliferation as detected by PCNA staining
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased apoptosis as detected by the TUNEL assay
Time frame: Baseline (randomization) to day 28
• Percent of subjects with 30% or greater decreased expression of the apoptotic protein Bcl-2
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased apoptosis as detected by cleaved caspase 3
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increase in DNA damage repair as detected by a reduction in γH2AX staining
Time frame: Baseline (randomization)to day 28
Percent of subjects with 30% or greater increased apoptosis as detected by DNA damage repair pathway proteins : p-γH2AX
Time frame: Baseline (randomization)to day 28
Percent of subjects with 30% or greater increased expression of the phosphorylated form of the DNA repair protein ATM
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein ATM.
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein RAD51.
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein ATR.
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response protein CHK1/2.
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater enhancement in the phosphorylation of DNA damage response proteins ATR.
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater decreased numbers of CD4+ T-cellscount
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased numbers of CD8+ T-cells
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater change in all trans-retinoic acid target genes : (ATRA) responsive genes (DHRS3, STRA6, MUC21, GABRP, DHRS9)
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater decreased expression of the immunological marker for regulatory T-cells, FoxP3
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased expression of the immunological marker for regulatory T-cells: IFN-γ
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased expression of the immunological marker for regulatory T-cells: IL-10
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater increased expression of the immunological marker for Th17 cells.
Time frame: Baseline (randomization) to day 28
Percent of subjects with 30% or greater decreased proliferation as detected by genes associated with immunological parameters: IL-22
Time frame: Baseline (randomization) to day 28
Number of subjects in each group with actinic keratosis at the end of treatment with UAB30 (day 28) and 84 days after the end of treatment with UAB30 (day 112).
Time frame: Baseline (randomization) to day 112
Mean number of toxicities experienced by subjects in each group treatment with UAB30 without signs of significant toxicity in organ transplant recipients..
Time frame: baseline to day 28
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
- Individual participant dataSharing planned: No
Related trials for Non-melanoma Skin Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Enrolling by invitationObservational study
Harvesting Cells for Experimental Cancer Treatments
Melanoma, Gastrointestinal Cancer
RecruitingPhase 1
Phase 1 Study of PF-08046033 in Advanced Solid Tumors
Non-Small-Cell Lung, Esophageal Cancer
Not yet recruiting
Gut Microbiome in Patients With Lung and Melanoma Cancer and Intestinal Microbiota in Gynecologic Cancers
Non Small Cell Lung Cancer, Melanoma (Skin Cancer)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Elmets, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing UAB30 in people with Non-melanoma Skin Cancer, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Baseline to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.