Clinical trial NCT05212246: Basal Cell Carcinoma Chemoprevention Trial
Official title: CSP #2019 - Basal Cell Carcinoma Chemoprevention Trial (B3C)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Basal Cell Carcinoma
Keywords: Basal Cell Carcinoma
chemoprevention
imiquimod
facial skin cancer
skin cancer prevention
squamous cell carcinoma
keratinocyte carcinoma
actinic keratosis
quality of life
side effects
treatment compliance
automated text messaging
cost comparison and cost effectiveness
implementation science
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2022-01-28
Enrollment: 1630
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is an intent-to-treat, parallel design, multicenter randomized trial and the primary intervention is a double-blind comparison of Imiquimod (IMQ) vs. placebo cream for preventing basal cell carcinoma (BCC) of the skin on the face at one year and over 3 years after therapy. Participants will apply the IMQ or placebo cream to the face daily at bedtime for 12 weeks. This study will recruit 1630 Veterans at high risk of BCC from 17 VA medical centers.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Veteran age 18 years or older
* 2 (or more) qualifying BCC lesions in the prior 5 years, with at least one located on the face, neck, ears, or scalp. "Qualifying lesions are those that meet the two inclusion criterion bullet points below, and none of the exclusion criteria listed in "B".
* Qualifying lesions not in a field of prior radiation therapy.
* Qualifying lesions not a recurrence after treatment, but the original lesion can qualify whether it recurred or not.

Exclusion Criteria:

* AK or KC field therapy on the face (5-FU cream, IMQ, diclofenac gel, chemical peel, or photodynamic therapy) for BCC treatment on the face in the last 2 months because it can cause inflammation that may interfere with the IMQ treatment. After 2 months, these patients can be included.
* IMQ therapy on the face in the past year, although such therapy in the more distant past is not an exclusion.
* Suspicious skin lesions suggestive of any type of skin cancer present on the face at the initial exam conducted for the study must be removed and have another skin exam to confirm the facial skin cancer is cleared for 1 month prior to randomization so that the investigators can be confident that skin cancer lesions that arise during the trial are new.
* Currently receiving or received in the past two months: immune checkpoint inhibitor, hedgehog pathway inhibitor, or oral capecitabine.
* History of cutaneous T-cell lymphoma within the past year, but low-grade prostate cancer, patch stage CTCL, breast cancer, and history of solid hematologic cancer deemed to be in remission will be included.
* Genetic disorder associated with very high basal cell skin cancer risk (i.e., basal cell nevus syndrome, xeroderma pigmentosum) because prevention efforts with IMQ may have dramatically different efficacy in these patients compared to the general high-risk population.
* Solid organ or bone marrow transplant recipient such as renal, hepatic, or cardiac transplant because these patients are at increased risk of KC (much greater risk of SCC than BCC) and the associated immunodeficiency may affect the effectiveness of IMQ
* Radiation therapy to the face
* Known allergy to IMQ or cream vehicle
* Woman currently pregnant or breast feeding
* Woman of childbearing potential unwilling to use birth control
* Judged by investigator to have a very high mortality risk within a year due to co-morbid illness
* Judged by investigator to be unlikely to comply with protocol requirements
* Judged by investigator not to be competent to provide informed consent
* Unable to communicate in English
* Enrolled in another therapeutic interventional trial

Primary outcomes:
measure: Proportion of participants with a new Basal Cell Carcinoma (BCC) on the face at 1 year
timeFrame: 1 year from the time of randomization
measure: Basal Cell Carcinoma (BCC) free time to a new BCC on the face over 3 years
timeFrame: 3 years from the time of randomization
Secondary outcomes:
measure: Proportion of participants with a new Squamous Cell Carcinoma (SCC) on the face at 1 year
timeFrame: 1 year from the time of randomization
measure: Squamous Cell Carcinoma (SCC) free time to a new SCC on the face over 3 years
timeFrame: 3 years from the time of randomization
measure: Total Actinic Keratosis (AK) reduction on the face over time during treatment and active follow-up
timeFrame: 3 years from the time of randomization
measure: AK reduction in each Olsen grade on the face over time during treatment and active follow-up
timeFrame: 3 year from the time of randomization
measure: Proportion of participants with any facial Actinic Keratosis (AK) biopsies or surgical removal on the face at 1 year
timeFrame: 1 year from the time of randomization
measure: Proportion of participants with a cheek or forehead primary Basal Cell Carcinoma (BCC) versus other areas of the face at 1 year
timeFrame: 1 year from the time of randomization
measure: Proportion of participants with a cheek or forehead primary Basal Cell Carcinoma (BCC) versus other areas of the face at 3 years
timeFrame: 3 years from the time of randomization
measure: Proportion of participants with a facial primary Basal Cell Carcinoma (BCC) of aggressive histologic subtypes at 1 year
timeFrame: 1 year from the time of randomization
measure: Proportion of participants with a facial primary Basal Cell Carcinoma (BCC) of aggressive histologic subtypes at 3 years
timeFrame: 3 years from the time of randomization
measure: Proportion of participants who have experienced a facial primary Basal Cell Carcinoma (BCC) of high severity at 1 year
timeFrame: 1 year from the time of randomization
measure: Proportion of participants who have experienced a facial primary Basal Cell Carcinoma (BCC) of high severity at 3 years
timeFrame: 3 years from the time of randomization
measure: Proportion of participants who have experienced a high or moderate severity facial primary Basal Cell Carcinoma (BCC) at 1 year
timeFrame: 1 year from the time of randomization
measure: Proportion of participants who have experienced a high or moderate severity facial primary Basal Cell Carcinoma (BCC) at 3 years
timeFrame: 3 years from the time of randomization
measure: Proportion of participants with any side effect of treatment during the treatment phase (weeks 1-13)
timeFrame: Weeks 1-13 after randomization
measure: Proportion of participants not tolerating the side effects during the treatment phase
timeFrame: Weeks 12 after randomization
measure: Facial photograph toxicity scores at week 6 and week 12
timeFrame: Weeks 6 and 12 after randomization
measure: Skindex-16 quality of life scores at 12 weeks
timeFrame: Twelve weeks after randomization
measure: Skindex-16 quality of life scores at 6 months
timeFrame: Six months after randomization
measure: Functional Assessment of Cancer Therapy-General (FACT-G) Physical Well-being score at 12 weeks
timeFrame: Twelve weeks after randomization
measure: Functional Assessment of Cancer Therapy-General (FACT-G) Physical Well-being score at 6 months
timeFrame: Six months after randomization
measure: Proportion of participants indicating acceptability of the study treatment cream at 12 weeks
timeFrame: Twelve weeks after randomization
measure: Study treatment compliance status during the 12 weeks of active treatment by treatment group
timeFrame: Twelve weeks after randomization
measure: Study treatment compliance status during the 12 weeks of active treatment by study site Annie application status
timeFrame: Twelve weeks after randomization
measure: Study treatment compliance status during the 12 weeks of active treatment by Annie application status only at sites offering Annie
timeFrame: Twelve weeks after randomization
measure: Proportion of participants with a new Basal Cell Carcinoma (BCC) on the face at 1 year by study treatment compliance status
timeFrame: One year after randomization
measure: Basal Cell Carcinoma (BCC) free time to a new BCC on the face over 3 years by study treatment compliance status
timeFrame: Three years from the time of randomization
Other outcomes:
Locations:
city: Providence
country: United States
facility: Providence VA Medical Center, Providence, RI
state: Rhode Island
Study officials:
affiliation: Providence VA Medical Center, Providence, RI
name: Martin A. Weinstock, MD
role: STUDY_CHAIR
References: