Basal Cell Carcinoma Chemoprevention Trial

Basal Cell Carcinoma (BCC) is the most common cancer in the United States. It afflicts 2 to 3 million Americans each year, more than all non-skin cancers combined. Notably, US active duty military and Veterans are at higher risk for developing BCC, with at least 49,000 Veterans treated for the disease in 2010. BCC usually occurs on the face and hence can result in high morbidity and disfigurement with substantial associated expense both in the overall population (estimated at $3 billion in 2013), and among Veterans (estimated at $86 million in 2012) served by Veterans Health Administration (VHA). Morbidity and disfigurement are particularly important due to their impact on key facial structures (e.g. eyelids, nose, etc). After BCC diagnosis, subsequent monitoring for BCC (ex. return specialist visits for dermatologic examinations) and treatments following diagnosis (surgeries most commonly, but also radiation therapy or chemotherapy) significantly contribute to healthcare costs. This large incidence, morbidity, and cost could potentially be minimized through preventative measures, but currently there are no treatment options for preventing BCC.

The primary goal of this study is to investigate the efficacy of topical Imiquimod (IMQ) for the prevention of BCC. IMQ, a topical immunostimulatory medication with a very low rate of side effects, is potentially capable of meeting this need. IMQ is already FDA approved as a safe and effective treatment for superficial BCC, as well as for actinic keratosis and nodular BCC. The investigators have reason to suspect that IMQ may also be able to prevent the occurrence of BCC or to destroy clinically-unrecognized precursors of BCC, thereby reducing the risk of BCC development.

CSP #2019 is an intent-to-treat, double-blind, parallel design, multicenter randomized trial of IMQ vs. placebo cream for preventing BCC on the face at one year and over 3 years after therapy. Nine out of 17 participating centers will start recruitment in the first year of the study (Phase 1 centers), with 5 centers randomly assigned to offer daily study treatment reminders via the Annie app and the other 4 centers not offering it. The remaining 8 centers (Phase 2 centers) will start in the second year of the study, with half of the centers randomized to offer daily study treatment reminders via the Annie app and the other half not offering it. Participants in each center will be randomly allocated (1:1) to either topical IMQ or placebo (vehicle control cream). Study participants, staff and study dermatologists will not know which treatment the participant receives. Participants will apply IMQ or placebo cream to the face daily at bedtime for a total of 12 weeks. In-person visits will occur at weeks 6 and 12 during treatment, and at months 6, 12, 18, 24, 30, and 36 during active follow-up to assess study outcomes. Full skin exams will be performed and other outcome data collected at every scheduled in-person visit with the exception that only facial skin exams are performed at weeks 6 and 12 visits. Telephone interviews will occur every week through week 13 (other than weeks 6 and 12, due to an in-person visit), as well as at months 9, 15, 21, 27, and 33. Follow-up will include 3 years of active follow-up with participants, followed by 1 year of passive follow-up during which study outcome information will only be captured from medical records.

• Proportion of participants with a new Squamous Cell Carcinoma (SCC) on the face at 1 year [Time frame: 1 year from the time of randomization]
• Squamous Cell Carcinoma (SCC) free time to a new SCC on the face over 3 years [Time frame: 3 years from the time of randomization]
• Total Actinic Keratosis (AK) reduction on the face over time during treatment and active follow-up [Time frame: 3 years from the time of randomization]
• AK reduction in each Olsen grade on the face over time during treatment and active follow-up [Time frame: 3 year from the time of randomization]
• Proportion of participants with any facial Actinic Keratosis (AK) biopsies or surgical removal on the face at 1 year [Time frame: 1 year from the time of randomization]
• Proportion of participants with a cheek or forehead primary Basal Cell Carcinoma (BCC) versus other areas of the face at 1 year [Time frame: 1 year from the time of randomization]
• Proportion of participants with a cheek or forehead primary Basal Cell Carcinoma (BCC) versus other areas of the face at 3 years [Time frame: 3 years from the time of randomization]
• Proportion of participants with a facial primary Basal Cell Carcinoma (BCC) of aggressive histologic subtypes at 1 year [Time frame: 1 year from the time of randomization]
• Proportion of participants with a facial primary Basal Cell Carcinoma (BCC) of aggressive histologic subtypes at 3 years [Time frame: 3 years from the time of randomization]
• Proportion of participants who have experienced a facial primary Basal Cell Carcinoma (BCC) of high severity at 1 year [Time frame: 1 year from the time of randomization]
• Proportion of participants who have experienced a facial primary Basal Cell Carcinoma (BCC) of high severity at 3 years [Time frame: 3 years from the time of randomization]
• Proportion of participants who have experienced a high or moderate severity facial primary Basal Cell Carcinoma (BCC) at 1 year [Time frame: 1 year from the time of randomization]