This study will evaluate the effectiveness of Aldara™ (Trademark) (Imiquimod) Cream in treating basal cell carcinoma (skin cancer).

Patients 18 years of age and older with an untreated suspected basal cell carcinoma may be eligible for this study.

First Visit:

Participants will have a medical history taken. A blood sample will be drawn and a doctor will examine, measure, and photograph the skin lesion. Two punch skin biopsies (surgical removal of a small piece of tissue for microscopic examination), will be taken from the area of the skin cancer, each less than 1/8th inch in diameter. One sample will be examined to confirm the diagnosis of basal cell carcinoma; the other will be sent to a laboratory for special tests that will be compared with another skin sample taken after treatment. In addition, a small amount of tissue will be removed from the area of skin cancer with a very fine needle. Patients will be shown how to apply the study cream and will be given a dosing kit with a supply of cream to take home. The cream contains either Aldara cream or a placebo (look-alike cream with no active ingredient).

Treatment Initiation

Patients will be randomly assigned to one of four treatment dosing groups. They will apply the cream as instructed in their kit according to one of the following schedules:

- Four doses, one dose every 12 hours, twice a day

- Four doses, one dose every 24 hours, once a day

- Eight doses, one dose every 12 hours, twice a day

- Eight doses, one dose every 24 hours, once a day

End-of-Treatment Visit

Patients will come to the clinic about 24 hours after their last dose for an end-of-treatment visit. A doctor will examine and photograph the skin cancer area. A second punch biopsy and fine needle aspiration will be taken and sent for special tests at a research laboratory. The doctor will then surgically remove the entire skin cancer and send it to a laboratory to be examined for skin cancer cells.

Upon starting treatment and at each clinic visit, participants will report any illnesses, side effects, or reactions to the study drug and will be asked about any medications they have taken.

Condition	Treatment or Intervention	Phase
Basal Cell Carcinoma	Drug: Imiquimod	Phase IV

Evaluation of the mechanism of action of Aldara ™ (Trademark) (Imiquimod, 1454-IMIQ) in the introduction of apoptotic and inflammatory changes when administered to Basal Cell Carcinoma in situ.

In this study, a collaboration between 3M, the US Navy and the Clinical Center of the National Institutes of Health will be entertained for the study of the mechanism(s) of action of a promising, new anti-cancer drug: Aldara ™ (Trademark) or Imiquimod. This drug can induce regression of several cancers when administered topically. Its effectiveness, when administered systemically is not clear as yet. Because the mechanism(s) of action of this drug is believe to be substantially different from that of common chemotherapeutic agents and it is believe to be due to immune modulation, it will be extremely important to understand the exact pathways adopted by this treatment to induce cancer regression. Through such understanding important information will be acquired not only about the specifics of this drug but also about how tumors are rejected by the immune system. Because tumor/immune system interaction occur in a dynamic fashion, several time points will need to be observed to understand the progression of events following administration of Imiquimod. Thus, a tumor model that is easily accessible will be necessary. In this case, we are interested in study the effect of Imiquimod on Basal Cell Carcinoma (BCC) because, being a skin cancer, it is easily accessible for biopsies and clinical observation. Patients with BCC will be identified at the Naval Hospital and randomly treated either with Imiquimod or with a placebo after signing informed consent. At the end of the established treatment all lesions will be removed for the study. Thus, in any case the patients will have their tumors removed and the end point of the study will not be to study the effectiveness of Imiquimod (that has been already established by previous studies). Patients will be stratified in different cohorts that will receive different treatment schedules paired by comparable treatments with placebo. Excision and biopsies of BCC will be preformed, therefore, at different time point since the beginning of treatment so that the progression of events occurring upon Imiquimod administration could be analyzed. The material obtained will be studies in the Immunogenetics Section of the Department of Transfusion Medicine, Clinical Center, National Institutes of Health. Tissues will be analyzed by immunohistochemistry, quantitative polymerase chain reaction and high-through genomic technologies to identify which proteins and/or genes are activated or turned off during this treatment. This will yield insight on the mechanism of action of Imiquimod and at the same about the major pathways adopted by the immune system to reject cancer. This information will in turn help the development of new strategies for the treatment of advanced cancers.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Subjects are eligible for the study if they meet all of the following criteria:
1. Willingness to give written informed consent prior to undergoing prestudy procedures specific to this study
2. Male or female
3. At least 18 years of age
4. Have at least one BCC lesion that meets the following criteria:
-Primary tumor (not recurrent or previously treated. The tumor may have been biopsied greater than 4 months prior to prestudy, but must not have been treated in any way.
-Qualifies, in the opinion of the investigator, for surgical excision as a primary therapy
-Located on the scalp, face (including ears), trunk, or proximal extremities
-Minimum diameter of 5 mm
-Histologically consistent with either superficial or nodular BCC (but not aggressive)
-Easily identifiable and treatable by the subject or reliable subject representative
EXCLUSION CRITERIA:
Subjects may not participate in this study if they have
1. Evidence of clinically significant or unstable medical condition(s) that would be expected to adversely affect either blood circulation or immune function
2. Had a febrile viral infection within 4 weeks of treatment initiation
3. Any dermatological disease at the treatment site that may be exacerbated by treatment with Imiquimod or cause difficulty with examination (eg, psoriasis, eczema)
4. Received any type of treatment to the target tumor
5. Received any cancer chemotherapy within 6 months before treatment initiation
6. Received any of the following treatment within 4 weeks before treatment initiation:
Interferon or interferon inducers
Immunomodulators or immunosuppressive therapies
Cytotoxic drugs
Investigational drugs
Oral corticosteriods
Inhaled corticosteriods (greater than 600 mcg/day for fluticasone or equivalent)
Topical steroids to the target tumor (Topical steroid use in locations other than the treatment area will be allowed during the study provided the amount used does not exceed 2-gm fluorinated steroids daily for greater than 1 week or 6 gm of beclomethasone for greater than 1 week.

Maryland
      Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020289; 02-CC-0289
Record last reviewed:  August 21, 2004
Last Updated:  August 21, 2004
Record first received:  September 11, 2002
ClinicalTrials.gov Identifier:  NCT00045851
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08