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Actinic KeratosisPhase 4NCT01229319

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

A Phase 4 study testing Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm in people with Actinic Keratosis, run by Frankel, Amylynne, M.D. at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Actinic Keratosis
What is being tested?
Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Oct 2010to Aug 2011
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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
  • topical corticosteroids if greater than 2 gm/day
  • any dermatologic procedures or surgeries on the study area (including any AK treatments)
  • Subjects who have used any topical prescription medications on the study area within 30 days prior to study treatment initiation.

Trial locations and contacts

1 site in 1 country.

Gary S Goldenberg, MD contact

212-241-3288

garygoldenbergmd@gmail.com

Giselle Singer, BS contact

212-241-3288

giselle.singer@mssm.edu

United States1 site, 1 recruiting
  • Mount Sinai School of Medicine, Department of Dermatology, Clinical Trials

    New York, New York, 10029

    Amylynne J Frankel, MD, 212-241-3288, amylynne.frankel@mssm.edu

    Giselle K Singer, BS, 212-241-3288, giselle.singer@mssm.edu

    Recruiting

Other trials in United States

About this study

Official title: An Investigator-Initiated Study to Assess the Safety and Efficacy of Imiquimod 3.75% Cream When Used After Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses (AK) on Dorsal Hands and Forearms

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%.

Read more

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.

Read the detailed description

Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet radiation exposure. Ultraviolet radiation produces local and systemic immunosuppression, mutations in the p53 tumor suppressor gene, and deoxyribonucleic acid pyrimidine covalent dimmers, each of which is believed to contribute to the dysplasia seen in AK. While most authorities consider AK as a pre-malignant lesion, some consider it as an incipient squamous cell carcinoma (SCC). The risk for progression to SCC for an individual AK is reportedly low but highly variable; however, as patients often have multplie AKs, the overall risk for progression over a lifetime can be significant; thus treatment of AKs is warranted. 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 provider-administered devices, temperature utilized, times of contact, and other variations in administration, influence efficacy of treatment. Efficacy can be improved by increasing the freeze time, but this is often associated with greater discomfort, more severe skin necrosis, and increased risk of post-treatment hypopigmentation. In addition, as with other lesion-directed therapies, cryosurgery does not treat subclinical lesions in the surrounding skin. Treated lesion clearance rates at 3 months post-treatment after double-freeze thaw cryotherapy has been reported to be around 76-88%; however, new lesions in the treatment field were not included. Overall lesion clearance rate, including new subclinical lesions, at approximately 5 months post-cryosurgery has been reported to be 35-51%. There is limited information on long-term AK clearance rates after cryosurgery and those reports differ in their methods of calculation. In a study comparing cyrotherapy, imiquimod and 5-fluorouracil, at 12 months post cryotherapy 28% (7/25) had complete clearance of baseline lesions that had undergone cryotherapy, but only 4% (1/25) had complete clearance of the treatment field.

Imiquimod is a topical immune response modifier that activates the innate immune system via Toll-like receptor 7, as well as enhances the acquired immune system. A 5% topical 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.

The imiquimod 5% formulation has limitations for the treatment of AKs. It is approved for the treatment of a small area of skin (25 cm2), uses a less than intuitive 2 times per week (2x/week) dosing schedule, and has a prolonged treatment period (16 weeks). Dosing more frequently than 3x/week with imiquimod 5% cream was not well tolerated in subjects with AK. 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.

Being tested
Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm
Keywords
actinic keratosis, keratocytic lesion, keratoses, cryotherapy, imiquimod
Medical subject headings
Keratosis, Actinic, Keratosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right armDrug

    Also called zyclara

    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

  • Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right armDrug

    Also called zyclara

    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

Study groups in NCT01229319
Study groupRoleWhat they receive
cryo + imiquimod to LeftExperimentalCryotherapy 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
Receives: Drug: Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm
Cryo + imiquimod to RightExperimentalCryotherapy 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
Receives: Drug: Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clearance of Actinic Keratoses

    AK lesion count, photography

    Measured: 14 weeks

Secondary outcomes (1)
  1. Local Skin Reactions (LSRs)

    Measured: 14 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionAug 2011 (estimated)
  4. Study completionAug 2011 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01229319
Sponsor's protocol ID
10-0933
Status last verified
Jun 2011
First submitted
26 Oct 2010
Last updated
22 Jun 2011
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cryotherapy alone to Left arm plus cryotherapy + imiquimod to Right arm in people with Actinic Keratosis, run by Frankel, Amylynne, M.D. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Gary S Goldenberg, MD (212-241-3288, garygoldenbergmd@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clearance of Actinic Keratoses (time frame: 14 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2011.

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