Basal Cell Carcinoma Chemoprevention Trial | NCT05212246

NCT05212246

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
5% Imiquimod Cream	Experimental	Topical 5% Imiquimod cream will be applied once daily to the face in a thin layer for 12 weeks. Three packets of cream will be defined as one dose or application. The cream should be applied to the face prior to normal sleeping hours (it is readily absorbed) and left on the skin for 6-10 hours (i.e. overnight). Rest periods will be allowed if bothersome side effects occur.	Drug: 5% Imiquimod cream
Placebo Vehicle Control Cream	Placebo Comparator	The placebo vehicle control cream will be a virtually identical cream (to the Imiquimod cream) that contains no Imiquimod. This cream will be applied once daily to the face in a thin layer for 12 weeks. Three packets of cream will be defined as one dose or application. The cream should be applied to the face prior to normal sleeping hours (it is readily absorbed) and left on the skin for 6-10 hours (i.e. overnight). Rest periods will be allowed if bothersome side effects occur.	Drug: Placebo Vehicle Control Cream

Interventions

Name	Type	Description	Arm Group Labels	Other Names
5% Imiquimod cream	Drug	Topical 5% Imiquimod cream will be applied once daily to the face in a thin layer for 12 weeks. Three packets of cream will be defined as one dose or application. The cream should be applied to the face prior to normal sleeping hours (it is readily absorbed) and left on the skin for 6-10 hours (i.e. overnight). Rest periods will be allowed if bothersome side effects occur.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of participants with a new Basal Cell Carcinoma (BCC) on the face at 1 year	Skin exams will occur at baseline and at 6-month intervals after study randomization. Diagnosis of a new BCC will be ascertained by a biopsy under local anesthesia in an outpatient setting, as is the standard of care. Every biopsy performed on the face of a participant during the trial will be processed per standard clinical operating procedures, as determined by their blinded clinician for the purposes of patient management. The biopsy will be sent for reading by a blinded central dermatopathologist with known high reliability (intra-rater and inter-rater with two other board-certified dermatopathologists) for diagnosing BCC. This central dermatopathologist diagnosis will be used for study purposes. Skin cancers diagnosed outside of the VA, and associated surgeries, will be systematically sought in all participants by participant interview and review of medical records to ensure that the outcome measure is complete.	1 year from the time of randomization
Basal Cell Carcinoma (BCC) free time to a new BCC on the face over 3 years	Basal Cell Carcinoma (BCC) free time to a new BCC on the face over 3 years is defined as the time in years from treatment randomization to the first occurrence of a new BCC on the face. Participants who do not develop a new BCC on the face by 3 years will be considered censored observations. Skin exams will occur at baseline and at 6-month intervals after study randomization.	3 years from the time of randomization

Secondary Outcomes

Measure	Description	Time Frame
Proportion of participants with a new Squamous Cell Carcinoma (SCC) on the face at 1 year	Diagnosis of a new SCC will be ascertained by a biopsy under local anesthesia in an outpatient setting, as is the standard of care. Every biopsy performed on the face of a participant during the trial will be processed per standard clinical operating procedures, as determined by their blinded clinician for the purposes of patient management, and the biopsy will also be sent for reading by a blinded central dermatopathologist with known high reliability (intra-rater and inter-rater with two other board-certified dermatopathologists) for diagnosing SCC. This central dermatopathologist diagnosis will be used for study purposes. Skin cancers diagnosed outside of the VA, and associated surgeries, will be systematically sought in all participants by participant interview and review of medical records to ensure that the outcome measure is complete.

Eligibility Module

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

Name	Role	Phone	Extension	Email
Kel G Morin	Contact	(347) 346-0380		Kel.Morin@va.gov

Name	Affiliation	Role
Martin A. Weinstock, MD	Providence VA Medical Center, Providence, RI	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Providence VA Medical Center, Providence, RI		Providence	Rhode Island	02908-4734	United States

IPD Sharing Statement Module

ID	Term
D002280	Carcinoma, Basal Cell
D002294	Carcinoma, Squamous Cell
D055623	Keratosis, Actinic
D010349	Patient Compliance

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms