Carcinoma, Basal CellPhase 2/3NCT02029352
Topical Green Tea Ointment in Treatment of Superficial Skin Cancer
A Phase 2/3 study testing Sinecatechins 10% in people with Carcinoma, Basal Cell, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Basal cell carcinoma (BCC) is the most frequently occurring nonmelanoma skin cancer in Caucasians, representing approximately 80% of cases. Incidence rates for men and women in the Netherlands are 165 and 157 per 100,000 person-years respectively and are still rising 3-10% annually. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Basal Cell
- What is being tested?
- Sinecatechins 10%
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2014to Feb 2016
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 years or older
- Primary histological proven superficial basal cell carcinoma ≥ 4mm and ≤ 20mm
- Comorbidities may not interfere with study treatment (evaluated by investigator)
- Capable to understand instructions
Who cannot join
- Recurrent sBCC (previous treatment)
- 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
- Tumour located in the H zone (high-risk area of face) or scalp
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Centre
Maastricht, Limburg, 6202 AZ
About this study
Official title: Topical Sinecatechins Ointment in Treatment of Primary Superficial Basal Cell Carcinoma: a Double Blind, Randomized, Placebo-controlled Trial.
Basal cell carcinoma (BCC) is the most frequently occurring nonmelanoma skin cancer in Caucasians, representing approximately 80% of cases. Incidence rates for men and women in the Netherlands are 165 and 157 per 100,000 person-years respectively and are still rising 3-10% annually. In 2009, the lifetime risk for developing a first histologically confirmed BCC for men was approximately 1 in 5 (21%) and for women it was 1 in 6 (18%).
A simplified classification of BCC includes the following three histological subtypes: nodular (40,6), superficial (30,7%) and infiltrative BCC (28,7%). Superficial BCCs (sBCCs) differ from the other subtypes as they tend to appear at a younger age, usually occur on the trunk and are often multiple. This subtype has the fastest growing incidence.
Read more
A characteristic feature of BCCs is their low risk to metastasize, though if untreated they may induce considerable functional and cosmetic morbidity as they are locally invasive. Surgery is the first treatment of choice for BCC. However due to the rising incidence and the extensive workload this entails, a non-invasive topical treatment is often chosen for sBCC as they grow down from the epidermis into the superficial dermis and therefore are easily accessible for topical treatment. Photodynamic therapy (PDT), imiquimod cream or 5-fluorouracil cream are available topical treatments for sBCC however their tumour free survival rates are not equal to the higher tumour free survival rates of surgical treatment. Next to the efficacy, the now available topical treatments are associated with local skin reactions at the treatment site, mainly erythema and erosion (imiquimod cream and 5-fluorouracil cream) or pain and burning sensation (PDT). This creates the need for additional or alternative non-invasive topical treatments.
The active constituents of green tea are promising as they are supported to have anti-BCC-carcinogenesis effects by several epidemiological, cell culture and animal studies. The so-called polyphenols known as catechins are the active constituents of green tea and the catechin epigallocatechin-3-gallate (EGCG) is the major and most active catechin. EGCG is thought to have a cytotoxic effect on skin cancer cells and has the availability of inhibition of cell growth and induction of apoptosis. It is also suggested that EGCG plays a role in inactivation of β-catenin signalling, an important component of the WNT pathway.
Sinecatechins 10% ointment (Veregen®) is a standardized extract of green tea leaves of the species Camellia sinensis, containing mainly green tea polyphenols, particularly catechins (more than 85%). The lead catechin in sinecatechins ointment is EGCG. It is approved by the US Food and Drug Administration (FDA) for genital warts in adults.
There are no clinical trials on human subjects with topical EGCG on sBCC yet. With this trial we are the first to try to validate the anti-carcinogenic potentials of topical EGCG in humans with sBCC. We assess the effectiveness of sinecatechins 10% (Veregen®) versus placebo for the topical treatment of sBCCs.
- Conditions
- Carcinoma, Basal Cell
- Being tested
- Sinecatechins 10%, Placebo
- Keywords
- Treatment, Sinecatechins
- Medical subject headings
- Carcinoma, Basal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sinecatechins 10%Drug
Also called Veregen
PlaceboDrug
Composition, apart from the active substance, is otherwise identical to the investigational medical product.
| Study group | Role | What they receive |
|---|---|---|
| Sinecatechins 10% | Experimental | Patients are instructed to apply a thin layer of the sinecatechins 10% ointment twice daily (morning and evening) in a thin layer to the tumour including 5mm of the surrounding skin. Before applying a new layer patients are advised to wipe off the remnants. Sinecatechins 10% ointment has to be applied for six weeks. Patients are advised to wash their hands after each application to prevent spreading of the ointment. Receives: Drug: Sinecatechins 10% |
| Placebo | Placebo comparator | Patients are instructed to apply a thin layer of the placebo ointment twice daily (morning and evening) in a thin layer to the tumour including 5mm of the surrounding skin. Before applying a new layer patients are advised to wipe off the remnants. Sinecatechins 10% ointment has to be applied for six weeks. Patients are advised to wash their hands after each application to prevent spreading of the ointment. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with complete histological clearance
Therapeutic surgical excision of the target tumour will be performed eight weeks after start of study treatment, for histological evaluation of response.
Measured: After 6 weeks treatment
Secondary outcomes (2)
Number of applications actually done by the patient divided by the total prescribed number of applications.
Measured: Week 6
Number of local skin reactions, adverse events and serious adverse events
Objective local skin signs (ie. Erythema, edema, induration, vesicles, erosion/ulceration, or other) will be assessed by the investigator at 3, 6 and 8 weeks after start of treatment.
Subjective symptoms (ie. Pain, burning, itching, or other) will be assessed from a personal diary kept by patients once a week during treatment.
Adverse events other than local skin reactions at the application site reported by the patient will be assessed according to the same grading.
Other adverse events or (suspected) (unexpected) serious adverse events will be recorded by the investigator.
Measured: Up to 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2014 (estimated)
- Study startNov 2014
- Primary completionSep 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Basal CellStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Will-Pharma, Medigene AG
- Responsible party
- Sponsor
- Investigators
- Nicole WJ Kelleners-Smeets, MD, PhD, Principal investigator, Maastricht University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02029352
- Sponsor's protocol ID
- NL47392.068.13
- Status last verified
- Jun 2015
- First submitted
- 18 Dec 2013
- Last updated
- 18 May 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Katiyar SK, Matsui MS, Elmets CA, Mukhtar H. Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol. 1999 Feb;69(2):148-53.
PubMed 10048310Singh T, Katiyar SK. Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting beta-catenin signaling. Toxicol Appl Pharmacol. 2013 Dec 1;273(2):418-24. doi: 10.1016/j.taap.2013.09.021. Epub 2013 Oct 3.
PubMed 24096034Tyring SK. Effect of Sinecatechins on HPV-Activated Cell Growth and Induction of Apoptosis. J Clin Aesthet Dermatol. 2012 Feb;5(2):34-41.
PubMed 22468171Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 1998 Apr;19(4):611-6. doi: 10.1093/carcin/19.4.611.
PubMed 9600345
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical Sinecatechins Ointment in Treatment of Primary Superficial Basal Cell Carcinoma: a Double Blind, Randomized, Placebo-controlled Trial.
- ClinicalTrials.gov ID
- NCT02029352
- Acronym / sponsor ID
- NL47392.068.13
- Conditions
- Carcinoma, Basal Cell
- Keywords
- Treatment, Sinecatechins
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Will-Pharma, Medigene AG
- Study start
- Nov 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 7 Jan 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 the most frequently occurring nonmelanoma skin cancer in Caucasians, representing approximately 80% of cases. Incidence rates for men and women in the Netherlands are 165 and 157 per 100,000 person-years respectively and are still rising 3-10% annually. In 2009, the lifetime risk for developing a first histologically confirmed BCC for men was approximately 1 in 5 (21%) and for women it was 1 in 6 (18%).
A simplified classification of BCC includes the following three histological subtypes: nodular (40,6), superficial (30,7%) and infiltrative BCC (28,7%). Superficial BCCs (sBCCs) differ from the other subtypes as they tend to appear at a younger age, usually occur on the trunk and are often multiple. This subtype has the fastest growing incidence.
A characteristic feature of BCCs is their low risk to metastasize, though if untreated they may induce considerable functional and cosmetic morbidity as they are locally invasive. Surgery is the first treatment of choice for BCC. However due to the rising incidence and the extensive workload this entails, a non-invasive topical treatment is often chosen for sBCC as they grow down from the epidermis into the superficial dermis and therefore are easily accessible for topical treatment. Photodynamic therapy (PDT), imiquimod cream or 5-fluorouracil cream are available topical treatments for sBCC however their tumour free survival rates are not equal to the higher tumour free survival rates of surgical treatment. Next to the efficacy, the now available topical treatments are associated with local skin reactions at the treatment site, mainly erythema and erosion (imiquimod cream and 5-fluorouracil cream) or pain and burning sensation (PDT). This creates the need for additional or alternative non-invasive topical treatments.
The active constituents of green tea are promising as they are supported to have anti-BCC-carcinogenesis effects by several epidemiological, cell culture and animal studies. The so-called polyphenols known as catechins are the active constituents of green tea and the catechin epigallocatechin-3-gallate (EGCG) is the major and most active catechin. EGCG is thought to have a cytotoxic effect on skin cancer cells and has the availability of inhibition of cell growth and induction of apoptosis. It is also suggested that EGCG plays a role in inactivation of β-catenin signalling, an important component of the WNT pathway.
Sinecatechins 10% ointment (Veregen®) is a standardized extract of green tea leaves of the species Camellia sinensis, containing mainly green tea polyphenols, particularly catechins (more than 85%). The lead catechin in sinecatechins ointment is EGCG. It is approved by the US Food and Drug Administration (FDA) for genital warts in adults.
There are no clinical trials on human subjects with topical EGCG on sBCC yet. With this trial we are the first to try to validate the anti-carcinogenic potentials of topical EGCG in humans with sBCC. We assess the effectiveness of sinecatechins 10% (Veregen®) versus placebo for the topical treatment of sBCCs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sinecatechins 10% | Experimental | Drug: Sinecatechins 10%Patients are instructed to apply a thin layer of the sinecatechins 10% ointment twice daily (morning and evening) in a thin layer to the tumour including 5mm of the surrounding skin. Before applying a new layer patients are advised to wipe off the remnants. Sinecatechins 10% ointment has to be applied for six weeks. Patients are advised to wash their hands after each application to prevent spreading of the ointment. |
| Placebo | Placebo comparator | Drug: PlaceboPatients are instructed to apply a thin layer of the placebo ointment twice daily (morning and evening) in a thin layer to the tumour including 5mm of the surrounding skin. Before applying a new layer patients are advised to wipe off the remnants. Sinecatechins 10% ointment has to be applied for six weeks. Patients are advised to wash their hands after each application to prevent spreading of the ointment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults aged 18 years or older
- Primary histological proven superficial basal cell carcinoma ≥ 4mm and ≤ 20mm
- Comorbidities may not interfere with study treatment (evaluated by investigator)
- Capable to understand instructions
Key exclusion criteria (6 listed)
- Recurrent sBCC (previous treatment)
- 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
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 |
|---|---|---|
| Sinecatechins 10%Also: Veregen | Drug | Sinecatechins 10% |
| PlaceboComposition, apart from the active substance, is otherwise identical to the investigational medical product. | Drug | Placebo |
Primary outcome
Percentage of patients with complete histological clearance
Time frame: After 6 weeks treatment
Therapeutic surgical excision of the target tumour will be performed eight weeks after start of study treatment, for histological evaluation of response.
2 secondary outcomes
Number of applications actually done by the patient divided by the total prescribed number of applications.
Time frame: Week 6
Number of local skin reactions, adverse events and serious adverse events
Time frame: Up to 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2016.
- Background: PubMed 10048310Katiyar SK, Matsui MS, Elmets CA, Mukhtar H. Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol. 1999 Feb;69(2):148-53.
- Background: PubMed 24096034Singh T, Katiyar SK. Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting beta-catenin signaling. Toxicol Appl Pharmacol. 2013 Dec 1;273(2):418-24. doi: 10.1016/j.taap.2013.09.021. Epub 2013 Oct 3.
- Background: PubMed 22468171Tyring SK. Effect of Sinecatechins on HPV-Activated Cell Growth and Induction of Apoptosis. J Clin Aesthet Dermatol. 2012 Feb;5(2):34-41.
- Background: PubMed 9600345Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 1998 Apr;19(4):611-6. doi: 10.1093/carcin/19.4.611.
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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.
Nicole WJ Kelleners-Smeets, MD, PhD principal investigator
Maastricht University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sinecatechins 10% in people with Carcinoma, Basal Cell, 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 6 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: finished, as of the sponsor's last update on 18 May 2016. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of patients with complete histological clearance (time frame: After 6 weeks 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 NCT02029352, which also lists 4 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 18 May 2016.