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

NCT02242929 | Unknown Phase 3 DMC

• 1 other identifier: NL50433.068.14
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

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.

Conditions

Nodular Basal Cell Carcinoma

Keywords

Nodular Basal Cell Carcinoma; Treatment; Imiquimod; Curettage; Surgery

Outcome Measures

Primary Outcomes (1)

• Proportion of participants tumour-free

  The primary study endpoint is the proportion of participants tumour-free at 1 year after end of treatment (defined as absence of initial treatment failure or any clinical signs of local recurrence). For SE, routine histological examination of haematoxylin and eosin (H\&E)-stained sections of the lateral and deep margins will be used to assess treatment failure. For curettage \& IMQ 5% cream, initial treatment failure will be clinically assessed at a follow-up visit 3 months after end of treatment. Initial treatment failure or any clinical signs of subsequent local recurrence will be assessed and recorded separately by one investigator. In case there is clinical suspicion of BCC, a 3 mm punch biopsy will be taken for histological verification.

  At 1 year after end of treatment

Secondary Outcomes (7)

• The 5-year cumulative probability of recurrence free survival after end of treatment

  At 5 years after end of treatment

• Compliance

  At 3 months after end of treatment

• Cosmetic appearance

  At 1 and 5 year after end of treatment

• Patient satisfaction

  At 1 and 5 year after end of treatment

• Level of Pain

  2 weeks after end of treatment

Other Outcomes (1)

• Baseline characteristics

  After inclusion visit

Study Arms (2)

Standard surgical excision

ACTIVE COMPARATOR

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

Procedure: Standard surgical excision

Imiquimod 5% cream with prior curettage

EXPERIMENTAL

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).

Drug: Imiquimod 5% cream with prior curettage

Interventions

Imiquimod 5% cream with prior curettage DRUG

Also known as: Aldara

Imiquimod 5% cream with prior curettage

Standard surgical excision PROCEDURE

Standard surgical excision

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University medical Centre

Maastricht, Limburg, 6202AZ, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 24332516 BACKGROUND

• Verkouteren BJA, Nelemans PJ, Sinx KAE, Kelleners-Smeets NWJ, Winnepenninckx VJL, Arits AHMM, Mosterd K. Imiquimod Cream Preceded by Superficial Curettage vs Surgical Excision for Nodular Basal Cell Carcinoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2025 Mar 1;161(3):299-304. doi: 10.1001/jamadermatol.2024.5572.

  PMID: 39878970 DERIVED

• 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.

  PMID: 32320773 DERIVED

MeSH Terms

Interventions

Imiquimod

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Klara Mosterd, MD, PhD

  Maastricht University Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2014
• First Posted: September 17, 2014
• Study Start: January 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2022
• Last Updated: September 24, 2021

Record last verified: 2021-09

Locations

NL (1)