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

Primary Purpose

Precancerous Condition

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
perillyl alcohol
placebo
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Precancerous Condition focused on measuring actinic keratosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arizona Cancer Center at University of Arizona Health Sciences Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

Low Dose POH 0.30%

High Dose POH 0.76%

Arm Description

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

Patients apply perillyl alcohol (POH) cream (0.3%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.

Patients apply perillyl alcohol (POH) cream (0.76%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.

Outcomes

Primary Outcome Measures

Change in Histopathology Score of Sun Damaged Skin by Treatment Group
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
The events do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. (NCI)

Full Information

First Posted
February 5, 2008
Last Updated
March 27, 2015
Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI), Arizona Disease Control Research Commission
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1. Study Identification

Unique Protocol Identification Number
NCT00608634
Brief Title
Topical Perillyl Alcohol in Treating Patients With Sun Damaged Skin and Actinic Keratoses
Official Title
Phase 2a Randomized, Placebo-Controlled, Double-Blind Trial of Topical Perillyl Alcohol in Sun Damaged Skin
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI), Arizona Disease Control Research Commission

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Precancerous Condition
Keywords
actinic keratosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
89 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients apply a placebo cream topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Arm Title
Low Dose POH 0.30%
Arm Type
Experimental
Arm Description
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 Title
High Dose POH 0.76%
Arm Type
Experimental
Arm Description
Patients apply perillyl alcohol (POH) cream (0.76%) topically to each dorsal forearm twice daily for 3 months in the absence of unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
perillyl alcohol
Intervention Description
Applied as topical cream
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Applied as topical cream
Primary Outcome Measure Information:
Title
Change in Histopathology Score of Sun Damaged Skin by Treatment Group
Description
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.
Time Frame
Baseline to 3 months
Secondary Outcome Measure Information:
Title
Skin Related Events From Perillyl Alcohol at Administered Doses by Participants
Description
The events do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. (NCI)
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steve Stratton, PhD
Organizational Affiliation
University of Arizona
Official's Role
Study Chair
Facility Information:
Facility Name
Arizona Cancer Center at University of Arizona Health Sciences Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724-5024
Country
United States

12. IPD Sharing Statement

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

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