Topical Perillyl Alcohol in Treating Patients With Sun Damaged Skin and Actinic Keratoses - Full Text View

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 Masking: Double-Blind 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:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by University of Arizona:

Primary Outcome Measures:

Change in histopathology grading [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety of perillyl alcohol at the administered doses [ Designated as safety issue: Yes ]
Statistically significant reductions in karyometric measurements (nuclear abnormality and discriminant function score) and biomarker expression (p53, apoptosis, and c-Fos) analyzed as percent immunohistochemical positive [ Designated as safety issue: No ]

Estimated Enrollment:	94
Study Start Date:	May 2004
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Arm I 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: Arm II 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: Arm III Patients apply POH cream (0.76%) as in arm II.	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 topically administered POH results in significant alterations in surrogate endpoint biomarkers of epidermal cell proliferation, including optical coherence tomography, p53 expression, c-Fos expression, and apoptosis (as measured by activated caspase-3 expression).
To determine if topically administered POH results in normalization of nuclear chromatin patterns in skin biopsy tissue from these patients, as determined by karyometric analysis.
To determine if topical POH can be administered safely to the forearms of these patients.

OUTLINE: Patients are randomized to 1 of 3 arms.

Arm I: Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Arm II: Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Arm III: 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 SCC or BCC in an area other than the test area are eligible upon excision of the SCC or BCC
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 SCC or BCC 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

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	Recruiting
Tucson, Arizona, United States, 85724-5024
Contact: Clinical Trials Office - Arizona Cancer Center at University o 520-626-9008

Sponsors and Collaborators

University of Arizona

National Cancer Institute (NCI)

Investigators

Study Chair:

Steve Stratton, MD

University of Arizona

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David Samuel Alberts, Arizona Cancer Center at University of Arizona Health Sciences Center
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
Last Updated:	September 17, 2010
Health Authority:	Unspecified

Keywords provided by University of Arizona:

actinic keratosis

Additional relevant MeSH terms:

Keratosis
Keratosis, Actinic
Precancerous Conditions
Skin Diseases
Neoplasms
Ethanol
Perilla alcohol
Anti-Infective Agents, Local
Anti-Infective Agents

Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013