Surgery Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma (SCIN)

Maastricht University Medical Centre (MUMC)

Status and phase: Unknown; Phase 3

Conditions: Nodular Basal Cell Carcinoma

Treatments: Drug: Imiquimod 5% cream with prior curettage; Procedure: Standard surgical excision

Study type: Interventional

Funder types: Other

Identifiers

NCT02242929

NL50433.068.14

Details and patient eligibility

About

Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant epidermal skin tumour. It is the most common malignant disease in Caucasians, representing approximately 80% of all cases of skin cancer and is therefore an important health problem. In the Netherlands incidence rates are 165 for men and 157 for women per 100.000 person-years, and these rates are rising with 3-10% every year.

A simplified histological classification of BCCs includes the following three subtypes: nodular, superficial and infiltrative variants, with the nodular variant being the most frequent type. Although a characteristic feature of BCCs is their low risk to metastasize, if untreated they may be locally invasive and may induce considerable functional and cosmetic morbidity.

The gold standard treatment of all histological BCC subtypes is surgical excision (SE), but not all patients are eligible for surgery. In patients with multiple BCCs and older patients, surgery may lead to significant morbidity, and in some cases, it may result in disfiguring scarring. For these reasons and to reduce workload and costs in the healthcare system, there is a growing demand for alternative, non-invasive, treatments. An advantage of non-invasive treatment options is that they can be performed by other healthcare professionals, such as general practitioners and specialized nurses. For treatment of superficial BCCs (sBCC) non-invasive treatments, such as topical imiquimod (IMQ), 5-fluorouracil (5-FU) or photodynamic therapy (PDT) are already commonly used. Our group investigated the efficacy of those three therapies and found that after 3 years, BCCs treated with IMQ had a significant lower risk of recurrence, compared to the other therapies.

A recent study suggests that IMQ, besides being an immune-response modifier, also directly inhibits sonic hedgehog (SHH) signalling, the most important pathway active in BCCs. This targeted effect of IMQ very likely explains the superior therapeutic effect. Treatment of nodular BCC (nBCC) with IMQ has been investigated. Without prior curettage, high efficacy rates were found, although efficacy was still slightly inferior to SE.

The investigators hypothesize that the effectiveness of IMQ following prior curettage will not be inferior to SE and that the benefits will be a higher patient satisfaction and lower healthcare costs. A recently published discreet choice experiment showed that patients preferred IMQ to surgery regardless of previous experience of BCC symptoms and treatment.

Enrollment: 145 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults aged 18 years or older
• Primary histologically proven nodular BCC ≥ 4mm and ≤ 20mm in diameter. (If the tumour exhibits additional sBCC characteristics, but also contains nodular component that extend into the reticular dermis, the tumour will be classified as nBCC with superficial components and will be included).
• Comorbidities may not interfere with study treatment
• Capable to understand instructions

Exclusion criteria

• A nodular BCC located in the H-zone of the face or hairy scalp
• Recurrent (previously treated) nBCC
• Aggressive BCC subtypes (morphoea, micronodular, or BCC with squamous differentiation)
• Life expectancy of less than five years
• Breast-feeding or pregnant women
• Serious comorbidities
• Use of immunosuppressive medication during the trial period or within 30 days before enrolment
• Patients with genetic skin cancer disorders

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

145 participants in 2 patient groups

Standard surgical excision

Active Comparator group

Description:

Standard surgical "elliptical" excision including a 3-mm clinically tumour-free margin according to the current local hospital arrangements.

Treatment:

Procedure: Standard surgical excision

Imiquimod 5% cream with prior curettage

Experimental group

Description:

Tumours will be partially debulked under local anaesthesia by removing all tumour tissue until normal dermis remains with a blunt curette. After curettage patients will receive an instruction sheet to apply imiquimod 5% cream once daily, 5 days a week, during 6 weeks, starting one week after the curettage procedure. Patients will be instructed to apply a thin layer to the tumour including 5-10mm of the surrounding skin at least 1 hour before going to bed at night. The lesion will not be covered (unless needed because of weeping or bleeding). Participants will be asked to wash their hands after applying the cream, and to wipe the cream off after 8 hours (in the morning).

Treatment:

Drug: Imiquimod 5% cream with prior curettage