Nodular Basal Cell CarcinomaPhase 3SCINNCT02242929
Surgery Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma
A Phase 3 study testing Imiquimod 5% cream with prior curettage and Standard surgical excision in people with Nodular Basal Cell Carcinoma, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Nodular Basal Cell Carcinoma
- What is being tested?
- Imiquimod 5% cream with prior curettage and Standard surgical excision
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2016to Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University medical Centre
Maastricht, Limburg, 6202AZ
About this study
Official title: Surgical Excision Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma: an Open, Non-inferiority, Randomized Controlled Trial
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.
Read more
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
- Being tested
- Imiquimod 5% cream with prior curettage, Standard surgical excision
- Keywords
- Nodular Basal Cell Carcinoma, Treatment, Imiquimod, Curettage, Surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imiquimod 5% cream with prior curettageDrug
Also called Aldara
Standard surgical excisionProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Standard surgical excision | Active comparator | Standard surgical "elliptical" excision including a 3-mm clinically tumour-free margin according to the current local hospital arrangements. Receives: 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). Receives: Drug: Imiquimod 5% cream with prior curettage |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 1 year after end of treatment
Secondary outcomes (7)
The 5-year cumulative probability of recurrence free survival after end of treatment
Any clinical signs of subsequent local recurrence will be assessed by one investigator. In case there is clinical suspicion of BCC, a 3 mm punch biopsy will be taken for histological verification.
Measured: At 5 years after end of treatment
Compliance
Data for compliance with the prescribed regimens of IMQ 5% cream will be obtained from a personal diary kept by patients and completed daily during the six week IMQ 5% application period in subjects allocated to treatment with IMQ. Compliance will be calculated as the number of applications actually applied by the patient divided by the total prescribed number of cream applications. Furthermore sachets will be collected and counted by the investigator. This is a separate compliance assessment. The number of returned sachets will be divided by the total prescribed number of sachets. During the phone consultation by the investigator two weeks after start of application, treatment will be evaluated to ensure continuation of treatment.
Measured: At 3 months after end of treatment
Cosmetic appearance
Cosmetic appearance of lesion site will be assessed independently by the participant and two independent investigators at 1 and 5 year follow-up using a Dutch four point scale and the Patient and Observer Scar Assessment Scale (POSAS).
Measured: At 1 and 5 year after end of treatment
Patient satisfaction
Patient satisfaction will be assessed by the participant at 1 and 5 year follow-up on the basis of 3 statements. For the extent of agreement a 4-point rating scale is used, ranging from total disagreement to total agreement
Measured: At 1 and 5 year after end of treatment
Level of Pain
The proportion of patients experiencing a moderate or more severe level of pain. In the IMQ 5 % group, this will be measured daily during the application period and 2 weeks after end of treatment. In the SE group, pain during SE procedure will be measured and pain until the removal of the stiches will be measured daily. Furthermore pain will be measured at the time of removal of the stiches. Pain will be assessed using a 10 cm Visual Analogue Scale (VAS) where 0 represents 'no pain' and 10 represents, 'most severe pain imaginable'.
Measured: 2 weeks after end of treatment
Cost-effectiveness
Data regarding resource use, i.e. outpatient visits, phone consultation, curettage, IMQ cream, SE and potential treatment of side-effects/adverse events will be recorded during the trial. Cost-prices will be derived from the manual for cost research in economic evaluations, the Pharmacotherapeutic Compass and the university hospital Maastricht. If necessary, cost-prices will be calculated based on real resource use. Total treatment costs will be estimated by multiplying volumes of use with the costs per unit. The cost-effectiveness ratio will be expressed as the incremental costs per additional tumour free patient. To quantify the uncertainty surrounding the incremental cost-effectiveness ratio (ICER) bootstrap analysis will be performed. Results of this analysis will be presented in cost-effectiveness planes and acceptability curves.
Measured: At 5 year after end of treatment
Adverse events
Adverse events, including local skin reactions, will be collected from all patients up to the 3 months follow-up visit and during phone consultation by the investigator (after two weeks of treatment in the IMQ group and during phone consultation about the histological examination of the excision specimen in the SE group). In case of an extra (phone) consultation of the patients as a result of severe adverse reactions, this will also be recorded. Serious events related to the investigative treatments (SUSAR) will be recorded during the entire follow-up period.
Measured: Up to 3 months after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2014 (estimated)
- Study startJan 2016
- Primary completionDec 2017
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Nodular Basal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Klara Mosterd, MD, PhD, Principal investigator, Maastricht University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02242929
- Sponsor's protocol ID
- NL50433.068.14
- Acronym
- SCIN
- Status last verified
- Sep 2021
- First submitted
- 15 Sep 2014
- Last updated
- 24 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24332516Verkouteren 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.
PubMed 39878970Sinx 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.
PubMed 32320773
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgical Excision Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma: an Open, Non-inferiority, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02242929
- Acronym / sponsor ID
- SCIN / NL50433.068.14
- Conditions
- Nodular Basal Cell Carcinoma
- Keywords
- Nodular Basal Cell Carcinoma, Treatment, Imiquimod, Curettage, Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Jan 2016 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2022 (estimated)
- First posted
- 17 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard surgical excision | Active comparator | Procedure: Standard surgical excisionStandard surgical "elliptical" excision including a 3-mm clinically tumour-free margin according to the current local hospital arrangements. |
| Imiquimod 5% cream with prior curettage | Experimental | Drug: Imiquimod 5% cream with prior curettageTumours 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). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imiquimod 5% cream with prior curettageAlso: Aldara | Drug | Imiquimod 5% cream with prior curettage |
| Standard surgical excision | Procedure or surgery | Standard surgical excision |
Primary outcome
Proportion of participants tumour-free
Time frame: At 1 year after end of treatment
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.
7 secondary outcomes
The 5-year cumulative probability of recurrence free survival after end of treatment
Time frame: At 5 years after end of treatment
Compliance
Time frame: At 3 months after end of treatment
Cosmetic appearance
Time frame: At 1 and 5 year after end of treatment
Patient satisfaction
Time frame: At 1 and 5 year after end of treatment
Level of Pain
Time frame: 2 weeks after end of treatment
Cost-effectiveness
Time frame: At 5 year after end of treatment
Adverse events
Time frame: Up to 3 months after end of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2021.
- Background: PubMed 24332516Bath-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.
- Derived from this study: PubMed 39878970Verkouteren 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.
- Derived from this study: PubMed 32320773Sinx 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klara Mosterd, MD, PhD principal investigator
Maastricht University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Imiquimod 5% cream with prior curettage and Standard surgical excision in people with Nodular Basal Cell Carcinoma, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants tumour-free (time frame: At 1 year after end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02242929, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2021.