Clinical trial NCT02242929: Surgery Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma
Official title: Surgical Excision Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma: an Open, Non-inferiority, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Nodular Basal Cell Carcinoma
Keywords: Nodular Basal Cell Carcinoma
Treatment
Imiquimod
Curettage
Surgery
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2014-09-17
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants tumour-free
timeFrame: At 1 year after end of treatment
Secondary outcomes:
measure: The 5-year cumulative probability of recurrence free survival after end of treatment
timeFrame: At 5 years after end of treatment
measure: Compliance
timeFrame: At 3 months after end of treatment
measure: Cosmetic appearance
timeFrame: At 1 and 5 year after end of treatment
measure: Patient satisfaction
timeFrame: At 1 and 5 year after end of treatment
measure: Level of Pain
timeFrame: 2 weeks after end of treatment
measure: Cost-effectiveness
timeFrame: At 5 year after end of treatment
measure: Adverse events
timeFrame: Up to 3 months after end of treatment
Other outcomes:
measure: Baseline characteristics
timeFrame: After inclusion visit
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University medical Centre
state: Limburg
Study officials:
affiliation: Maastricht University Medical Centre
name: Klara Mosterd, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bath-Hextall F, Ozolins M, Armstrong SJ, Colver GB, Perkins W, Miller PS, Williams HC; Surgery versus Imiquimod for Nodular Superficial basal cell carcinoma (SINS) study group. Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):96-105. doi: 10.1016/S1470-2045(13)70530-8. Epub 2013 Dec 11.
citation: Sinx KAE, Nelemans PJ, Kelleners-Smeets NWJ, Winnepenninckx VJL, Arits AHMM, Mosterd K. Surgery versus combined treatment with curettage and imiquimod for nodular basal cell carcinoma: One-year results of a noninferiority, randomized, controlled trial. J Am Acad Dermatol. 2020 Aug;83(2):469-476. doi: 10.1016/j.jaad.2020.04.053. Epub 2020 Apr 19.