Topical Perillyl Alcohol in Treating Patients With Sun Damaged Skin and Actinic Keratoses

This study has been completed.
Sponsor:
Collaborators:
Arizona Disease Control Research Commission
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00608634
First received: February 5, 2008
Last updated: March 27, 2015
Last verified: March 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as perillyl alcohol, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. It is not yet known which dose of topical perillyl alcohol is more effective in stopping the development of cancer in sun damaged skin.

PURPOSE: This randomized phase II trial is studying high-dose topical perillyl alcohol to see how well it works compared with low-dose topical perillyl alcohol in treating patients with sun damaged skin and actinic keratoses.


Condition Intervention Phase
Precancerous Condition
Drug: perillyl alcohol
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2a Randomized, Placebo-Controlled, Double-Blind Trial of Topical Perillyl Alcohol in Sun Damaged Skin

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Change in Histopathology Score of Sun Damaged Skin by Treatment Group [ Time Frame: Baseline to 3 months ] [ Designated as safety issue: No ]
    The histopathologic scoring for skin biopsies from sun-damaged skin to assess the following seven characteristics: 1- atypia (levels 0, 1 & 2), 2- inflammation (grades 0, 1 & 2), 3- hyperkeratosis (loss of basket weave pattern of stratum corneum), 4- parakeratosis (present when there were >3 characteristic nuclei per 40:1 field in stratum corneum), 5- dyskeratosis (focal presence of cells with homogenous, pink cytoplasm n pyknotic nuclei), 6- epidermotropism (lymphocytes migration of >3 cells into epidermis, 7- loss of granular layer. All assessments were done using a 40:1 objective.


Secondary Outcome Measures:
  • Skin Related Events From Perillyl Alcohol at Administered Doses by Participants [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    The events do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. (NCI)


Enrollment: 89
Study Start Date: May 2004
Study Completion Date: June 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Other: placebo
Applied as topical cream
Experimental: Low Dose POH 0.30%
Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Drug: perillyl alcohol
Applied as topical cream
Experimental: High Dose POH 0.76%
Patients apply perillyl alcohol (POH) cream (0.76%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Drug: perillyl alcohol
Applied as topical cream

Detailed Description:

OBJECTIVES:

Primary

  • To determine if topical administration of perillyl alcohol (POH) cream can reverse actinic damage as evidenced by normalization of quantitative skin histopathology scores in skin tissue biopsy samples from patients with moderate to severe sun damage.

Secondary

  • To determine if topical POH can be administered safely to the forearms of these patients.

OUTLINE: Patients are randomized to 1 of 3 arms.

  • Placebo: Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
  • Low Dose: Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
  • High Dose: Patients apply POH cream (0.76%) as in arm II. Patients undergo tissue sampling of the right or left dorsal forearm and of physician-selected representative actinic keratoses (AK) at baseline and after completion of study therapy. Tissue samples are assessed for changes in patterns of biomarker expression (i.e., p53, apoptosis, c-Fos histopathology) and karyometry. After completion of study therapy, patients undergo tissue sampling of the opposite forearm as well as blood sample collection to determine perillyl alcohol (POH) levels in blood and biopsy samples. Urine is also collected and analyzed for safety at the end of treatment. Digital photographs of the forearms and hands are obtained at baseline and after 3 months of study treatment. Optical coherence tomography imaging is also performed on pre- and post-biopsy sites to quantify the effect of POH on sun damage and AK in skin.

After completion of study treatment, patients are followed monthly.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Resident of Pima or adjoining Southern Arizona county

    • Patients outside of Pima County are also eligible
  • Sun damaged skin as judged by the study physician and quantifiable, clinically diagnosed, and visible actinic keratoses (AK) on both dorsal forearms, with at least two AK on each arm

    • AK lesions must not be clustered, confluent, or too numerous to count accurately
    • Presence of AK on sites other than the test area allowed
  • No significant inflammation or irritation of the skin of the upper extremities that is not clinically diagnosed as sun damage or AK
  • Patients must agree to limit sun exposure as much as possible and may continue their normal pattern of sunscreen use

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Females must not be of childbearing potential, and therefore must be post-menopausal or surgically sterile by hysterectomy
  • Not pregnant or nursing

Exclusion criteria:

  • Concurrent skin malignancy or disorder of the upper extremities

    • Patients with Squamous cell carcinoma or basal cell carcinoma in an area other than the test area are eligible upon excision of the Squamous cell carcinoma or basal cell carcinoma
  • Patients who are immunosuppressed by virtue of medication or disease
  • Serious concurrent illness that could interfere with study regimen
  • Invasive cancer within the past 5 years

PRIOR CONCURRENT THERAPY:

  • At least 30 days since prior topical medications to the skin of the upper extremities except for emollients or sunscreens
  • At least 30 days since prior and no concurrent mega-doses of vitamins, defined as any of the following:

    • More than 5 times the recommended daily allowance
    • More than 5 capsules of multivitamins
    • 400 IU of vitamin E
    • 200 μg of selenium
    • 1 gm of vitamin C
  • At least 6 months since prior and no concurrent therapy for squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) anywhere in the test area (i.e., the forearms or hands)

    • Treatment for Squamous cell carcinoma or basal cell carcinoma on sites other than the test area is allowed
  • At least 4 weeks since prior surgical biopsy, surgical excision, or cryotherapy for AK in the test area and the sites must have healed
  • At least 6 months since prior topical treatment (e.g., 5-fluorouracil or imiquimod) for AK
  • No concurrent therapy that may interfere with clinical evaluations
  • No concurrent topical drug treatment (e.g., retinoids, aminolevulinic acid, diclofenac sodium, imiquimod, or fluorouracil) to any area of skin, including test area
  • No concurrent enrollment in another clinical trial
  • No concurrent topical citrus peel or consumption of citrus peel
  • No chemotherapy for cancer within the past 5 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608634

Locations
United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
Sponsors and Collaborators
University of Arizona
Arizona Disease Control Research Commission
Investigators
Study Chair: Steve Stratton, PhD University of Arizona
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00608634     History of Changes
Other Study ID Numbers: CDR0000582634, P01CA027502, P30CA023074, UARIZ-HSC-04-27, UARIZ-POH-002
Study First Received: February 5, 2008
Results First Received: April 15, 2011
Last Updated: March 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
actinic keratosis

Additional relevant MeSH terms:
Precancerous Conditions
Neoplasms
Ethanol
Perilla alcohol
Anti-Infective Agents
Anti-Infective Agents, Local
Antineoplastic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015