Imiquimod 3.75% Cream in Combination With Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses

NCT01229319 | Unknown Phase 4 DMC

• 1 other identifier: 10-0933
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet radiation exposure. While most authorities consider AK as a pre-malignant lesion, some consider it as an incipient squamous cell carcinoma (SCC). In addition, the skin around clinically obvious AK lesions has been subject to the same chronic ultraviolet exposure, resulting in genetic damage and mutations, resulting in "field cancerization." Subclinical AKs may progress to clinical AKs, or even de novo invasive SCCs. Among the current therapies for the treatment of AK are excisional surgery, cryosurgery, electrodessication and curettage, topical chemotherapy and light therapies. With cryotherapy, treated lesion clearance rates at 3 months post-treatment after double-freeze thaw cryotherapy has been reported to be around 76-88%; Overall lesion clearance rate at approximately 5 months post-cryosurgery has been reported to be 35-51%. Imiquimod is a topical immune response modifier and a 5% formulation has been approved for the treatment of AKs in the US as a 2x/week for 16 week regimen and in Europe as a 3x/week for 4 week regimen for 1 or 2 courses of therapy. Topical imiquimod treatment may also reduce subclinical lesions in the treatment area, resulting in fewer "new" AK lesions developing over the same period of time when compared to focal treatment. In a comparison of cryosurgery versus imiquimod for the treatment of AKs, Krawtchenko et al reported initial complete clearance rates of 68 and 85% by clinical assessment, respectively. However, the treatment field sustained clearance rate was 4% versus 73%, respectively. Tan et al reported that while application of imiquimod or vehicle following cryosurgery resulted in comparable target AK clearance rates at 12 weeks of 79% versus 76%, respectively, the imiquimod group had fewer total AKs and fewer subclinical AKs. Imiquimod cream at a concentration of 3.75% has been found in Phase 3 studies to be superior to placebo cream with respect to clearance of AKs using a regimen of up to 2 packets (250 mg of cream per packet, 500 mg total) applied daily to the entire face (approximately 200 cm2) for two 2-week treatment cycles separated by a 2-week no-treatment period. This study aims to examine the benefit of cryotherapy in combination with imiquimod 3.75% compared to cryotherapy alone.

Conditions

Actinic Keratosis

Keywords

actinic keratosis, keratocytic lesion, keratoses, cryotherapy, imiquimod

Outcome Measures

Primary Outcomes (1)

• Clearance of Actinic Keratoses

  AK lesion count, photography

  14 weeks

Secondary Outcomes (1)

• Local Skin Reactions (LSRs)

  14 weeks

Study Arms (2)

cryo + imiquimod to Left

EXPERIMENTAL

Cryotherapy alone to Right arm plus cryotherapy + imiquimod 3.75% daily x 2 weeks on and 2 weeks off and 2 weeks on to Left arm

Drug: Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm

Cryo + imiquimod to Right

EXPERIMENTAL

Cryotherapy alone to Left arm plus cryotherapy + imiquimod 3.75% daily x 2 weeks on and 2 weeks off and 2 weeks on to Right arm

Drug: Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm

Interventions

Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm DRUG

Cryotherapy alone to Left arm plus cryotherapy + imiquimod 3.75% daily x 2 weeks on and 2 weeks off and 2 weeks on to Right arm

Also known as: zyclara

cryo + imiquimod to Left

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults at least 18 years old.
• Subjects must be in good general health as confirmed by the medical history.
• Subjects must be able to read, sign, and understand the informed consent
• Prior to cryosurgery, subjects have at least 3 hypertrophic actinic keratoses on each dorsal hand/forearm.
• Subject must be willing to forego any other treatments on the dorsum of the hands and or/forearms, including tanning bed use and excessive sun exposure while in the study.
• Subject is willing and able to participate in the study as an outpatient, making frequent visits to the study center during the treatment and follow-up periods and to comply with all study requirements including concomitant medication and other treatment restrictions.
• If subject is a female of childbearing potential she must have a negative urine pregnancy test result prior to study treatment initiation and must agree to use an approved method of birth control while enrolled in the study.

You may not qualify if:

• Subjects with a history of melanoma anywhere on the body.
• Subjects with an unstable medical condition as deemed by the clinical investigator.
• Subjects with non-melanoma skin cancer on the dorsum of the hands or forearms.
• Subjects with any dermatologic disease in the treatment area that may be exacerbated by the treatment proposed or that might impair the evaluation of AKs.
• Subjects who have previously been treated with imiquimod: on the dorsum of the hands or forearms in the past 6 months; or outside of the study area within the past 30 days.
• Women who are pregnant, lactating, or planning to become pregnant during the study period.
• Subjects who have experienced a clinically important medical event within 90 days of the visit (e.g., stroke, myocardial infarction, etc).
• Subjects who have active chemical dependency or alcoholism as assessed by the investigator.
• Subjects who have known allergies to any excipient in the study cream.
• Subjects who are currently participating in another clinical study or have completed another clinical study with an investigational drug or device on the study area within 30 days prior to study treatment initiation.
• Subjects who have received any of the following within 90 days prior to study treatment initiation:
• interferon or interferon inducers
• cytotoxic drugs
• immunomodulators or immunosuppressive therapies (inhaled/ intranasal steroids are permitted)
• oral or parenteral corticosteroids

Sponsors & Collaborators

• Frankel, Amylynne, M.D.: lead
• Graceway Pharmaceuticals, LLC: collaborator

Study Sites (1)

Mount Sinai School of Medicine, Department of Dermatology, Clinical Trials

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Keratosis, Actinic; Keratosis

Interventions

Cryotherapy; Imiquimod

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gary S Goldenberg, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gary S Goldenberg, MD

CONTACT

212-241-3288; garygoldenbergmd@gmail.com

Giselle Singer, BS

CONTACT

212-241-3288; giselle.singer@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 26, 2010
• First Posted: October 27, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 22, 2011

Record last verified: 2011-06

Locations

US (1)