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

NCT ID: NCT00608634

Last Updated: 2015-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2009-06-30

Brief Summary

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.

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.

Conditions

Precancerous Condition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Applied as topical cream

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.

Group Type: EXPERIMENTAL

perillyl alcohol

Intervention Type: DRUG

Applied as topical cream

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.

Group Type: EXPERIMENTAL

perillyl alcohol

Intervention Type: DRUG

Applied as topical cream

Interventions

perillyl alcohol

Applied as topical cream

Intervention Type: DRUG

placebo

Applied as topical cream

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Arizona Disease Control Research Commission

OTHER_GOV

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Stratton, PhD

Role: STUDY_CHAIR

University of Arizona

Locations

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Countries

United States

Other Identifiers

P01CA027502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA023074

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UARIZ-HSC-04-27

Identifier Type: OTHER

Identifier Source: secondary_id

UARIZ-POH-002

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000582634

Identifier Type: -

Identifier Source: org_study_id