Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Carcinoma

Prostatic Neoplasms

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Neuroprotective Agents

All Drugs and Chemicals

Herbal and Botanical

Flavonoid

Other Dietary Supplements

Epigallocatechin gallate

Catechin

Epicatechin

Patients receive green tea catechins PO BID for up to 6 months in the absence of disease progression or unacceptable toxicity.

Patients receive placebo PO BID for up to 6 months.

Placebo Administration

Quality-of-Life Assessment

Questionnaire Administration

Sinecatechins

Site Public Contact

Nicholas DiBella

Shahzad Siddique

Jay W. Carlson

Edward J. Kim

Lisa Bailey

Bradley C. Ekstrand

Jessica D. McDermott

Paul D. Maroni

Mike Cusnir

Tareq Al Baghdadi

Prem Sobti

Bryan A. Faller

Thomas E. Lad

Nagi B Kumar

This phase II trial studies how well green tea catechins work in preventing progression of prostate cancer from a low risk stage to higher risk stages in men who are on active surveillance. Green tea catechins may stabilize prostate cancer and lower the chance of prostate growing.

PRIMARY OBJECTIVE:

I. To compare the change in the percent (%) Ki-67 expression in a biopsy core positive for cancer from baseline to end-of-study (EOS) biopsy between men on active surveillance (AS) for prostate cancer (PCa), treated with green tea catechins (GTCs) or placebo for 6 months.

SECONDARY OBJECTIVES:

I. To assess apoptosis by caspase in tumor tissue from EOS biopsy by treatment. II. To assess % Ki-67: Apoptosis ratio from EOS biopsy by treatment. III. To evaluate the number of biopsy cores positive for cancer from EOS biopsy by treatment.

IV. To evaluate the percentage of any biopsy tissue core positive for cancer from EOS biopsy by treatment.

V. To evaluate % Ki-67 in EOS biopsy from the same quadrant matching the quadrant with the highest % Ki-67 at baseline treatment.

VI. To evaluate the Gleason sum from EOS biopsy by treatment. VII. To evaluate the change in serum prostate-specific antigen (PSA) from baseline to 3 months and to EOS by treatment.

VIII. To evaluate the safety of 6 month administration of GTC assessed by Common Toxicity Criteria (CTC) version 5.0, complete blood count (CBC), comprehensive metabolic panel (CMP) and liver function toxicities (LFTs) by treatment.

IX. To evaluate the change in geometric mean of % Ki-67 measures in all the cores positive for cancer from baseline to EOS biopsy by treatment.

EXPLORATORY OBJECTIVES:

I. To evaluate the change in catechin (epigallocatechin gallate \[EGCG\]) as indicated by change from EGCG measured in plasma from baseline and EOS by treatment.

II. To evaluate the adherence and acceptability to GTC based on the percentage compliance using agent logs (%) and pill counts monthly until EOS by treatment groups.

III. To evaluate the bioavailability of GTC as indicated by change from EGCG measured in plasma from baseline and EOS by treatment groups.

PATIENT REPORTED OUTCOMES OBJECTIVES:

I. To evaluate the change in lower urinary tract symptoms (LUTS) from baseline to 3 months and to EOS using the LUTS scale by treatment groups.

II. To evaluate the change in quality of life (QOL) scores from baseline to 3 months and to EOS using the Functional Assessment of Cancer Therapy (FACT)-Prostate by treatment groups.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive green tea catechins orally (PO) twice daily (BID) for up to 6 months in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive placebo PO BID for up to 6 months.

After completion of study, patients are followed up at approximately 7 days, at 6 months, and then up to 12 months.

To Evaluate if Green Tea Can be Effective in Reducing the Progression of Prostate Cancer in Men on Close Monitoring

A Phase II Randomized Double Blinded Study of Green Tea Catechins (GTC) vs. Placebo in Men on Active Surveillance for Prostate Cancer: Modulation of Biological and Clinical Intermediate Biomarkers

Compliance to study drug will be evaluated by standard pill counts. Will evaluate percentage compliance to study agent in the study arms using pill counts.

Compliance to study drug will be evaluated by diet records.

Compliance to study drug will be evaluated by plasma concentrations of GTC (epigallocatechin gallate \[EGCG\]). For plasma, will assess the change from baseline to end of treatment for GTC (EGCG) to estimate compliance and bioavailability.

Will correlate EGCG concentrations with prostate specific antigen density (PSAD) and prostate specific antigen doubling time (PSADT), using descriptive analysis with scatter plots and regression analysis, and adjusting intervention and known predictors including the stratification factors in multivariable analysis. Will transform to the square root or logarithmic transformation of the data to improve normality of the distributions (determined as the transformation (including untransformed) with the lowest Anderson-Darling normality score).

Lower urinary tract symptoms (LUTS) will be assessed using the American Urological Association Symptom Score for the evaluation, LUTS Symptom Scale. The highest score on the scale is 5, "almost always" and the lowest score on the scale is 0, "not at all".

Will assess change in EGCG from baseline to EOS, adherence to GTC, and bioavailability of GTC from baseline to EOS by treatment.

Quality of life will be assessed using the Functional Assessment of Cancer Therapy (FACT)-Prostate.

Measured in a core positive for tumor from baseline to highest percent (%) Ki-67 expression measured in a core positive for tumor in the end of study (EOS) biopsy. This change will be compared between green tea catechins (GTC) and placebo arms. The highest % Ki-67 expressions from baseline and EOS biopsies will be used to estimate the change. If the change is not normally distributed, non-parametric test such as Wilcoxon-rank sum test or two-sample normal score test will be used to compare the changes in percent Ki-67 levels between the GTC and placebo arms.

Will be assessed by caspase in tumor tissue from EOS biopsy by treatment.

Will be evaluated from EOS biopsy by treatment groups. Descriptive statistics with confidence intervals will be presented. For continuous measures, will use two-sample t-test or Wilcoxon rank sum test (if non-parametric test is more appropriate) to compare the measurements by treatment.

Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test.

Descriptive statistics with confidence intervals will be presented. For continuous measures, will use two-sample t-test or Wilcoxon rank sum test (if non-parametric test is more appropriate) to compare the measurements by treatment.

Will use three mixed models (for PSA, PSA doubling time, and PSA density). For the first two, will log the PSA value. For PSA, will have intercepts and slopes for each patient, an unstructured covariance model, and 2 terms for the intercept and slope associated with the treatment group. For the PSA doubling time, will center the baseline values at 1, and estimate the slopes for each patient (from which the doubling time can be derived), along with a net slope effect for the treatment group. The mixed model for PSA density will be analogous to the one for PSA.

Will be assessed by Common Toxicity Criteria version 5.0, complete blood count, comprehensive metabolic panel, and liver function toxicities by treatment. All toxicity data will be summarized by category and grade in a standard fashion. Proportions experiencing the most common types of toxicity in this trial will be estimated and 95% confidence intervals calculated. Adverse event rates (such as worst grade 3 or higher) by arm will be estimated and compared.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Skin and Connective Tissue Diseases

Skin Neoplasms

Carcinoma, Basal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Basal Cell

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.

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.

Sinecatechins 10%

Composition, apart from the active substance, is otherwise identical to the investigational medical product.

Placebo

Nicole WJ Kelleners-Smeets, MD, PhD

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.

Topical Green Tea Ointment in Treatment of Superficial Skin Cancer

Topical Sinecatechins Ointment in Treatment of Primary Superficial Basal Cell Carcinoma: a Double Blind, Randomized, Placebo-controlled Trial.

Therapeutic surgical excision of the target tumour will be performed eight weeks after start of study treatment, for histological evaluation of response.

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.

Will-Pharma

Medigene AG

Maastricht University Medical Center

Infections

Warts

Condylomata Acuminata

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Cryotherapy and then Sinecatechins 15% Ointment 1 week later.

Cryotherapy will be standardized in all subjects and for all treated lesions: EGW lesions will be treated with 2 sprays, 5 seconds each, with a 5 second interval. All subjects will be treated with the same cryo-spray regimen.

Following cryotherapy, half of the subjects will be randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy (Week 1).

Sinecatechins 15% Ointment

Cryotherapy will be standardized in all subjects and for all treated lesions.

Cryotherapy alone

Gary Goldenberg, MD

External Genital Warts (EGW) are the most common sexually transmitted disease associated with more than 30 types of the Human Papillomavirus (HPV). Cryotherapy is an effective method of EGW treatment. However, multiple sessions may be required with reported clearance rates ranging between 27-88%. Sinecatechins 15% ointment is Food and Drug Administration approved for three times daily application in immunocompetent subjects 18 years and older for the treatment of EGW and perianal warts. Treatment of EGW with cryotherapy followed by sinecatechins appears to be logical. Cryotherapy has direct cytodestructive effects with immediate short-term efficacy on treated EGW, while sinecatechins provide field therapy, treating both clinical and sub-clinical lesions. For this study, the investigators used sinecatechins 15% ointment twice daily regimen and anticipated that the synergistic effect with cryotherapy will provide better efficacy that cryotherapy alone. The investigators also anticipated that the sequential therapy with be safe.

A total of 42 subjects received standardized cryotherapy to all lesions, using two cycles of five seconds each, separated by a five second interval rest (Week 0/Baseline). One week following cryotherapy, subjects were randomized 1:1 to either additional treatment with sinecatechins 15% ointment twice daily or no additional treatment. Those subjects randomized to additional treatment received sinecatechins 15% ointment BID for up to sixteen weeks, or until complete clearance of all EGW, whichever occurred first. Additionally, subjects were advised to maintain safe sexual practices and have all recent sexual partners examined for EGW. Subjects were followed every 8 weeks for a total of 16 weeks (Table 1). EGW lesion counts were conducted at all study visits by the same qualified blinded evaluator. Additionally, at each visit local skin reactions, change in concomitant medications, and adverse events were assessed. Any subjects who received sinecatechins 15% ointment and discontinued prematurely were asked to return for an End of Study Visit. Females of childbearing potential underwent a urine pregnant test at all visits during study treatment period. Subjects that met complete responder criteria as above, were additionally followed and assessed at Visit5/Week 41 and Visit 6/Week 65 to assess for wart recurrence.

Treatment of External Genital Warts With Cryotherapy and Sinecatechins 15% Ointment

An Investigator-Initiated Study to Assess the Safety and Efficacy of Sinecatechins 15% Ointment When Used in Conjunction With Cryotherapy in the Treatment of External Genital Warts

Subjects with complete clearance, or no longer have HPV infected cells. Complete clearance was defined as zero lesions at the respective time points.

To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 24 week post-treatment period.

To evaluate the efficacy of using combination cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone on EGW lesions via recurrence rates of previously treated EGW lesions in those subjects who achieved a complete response over a 48 week post-treatment period.

To evaluate the safety of cryotherapy-sinecatechins 15% ointment BID versus cryotherapy alone as a regimen for EGW by evaluating for local skin reactions and adverse events.

Number of participants with local skin reactions.

Partial clearance is described as at least 50% reduction from baseline

Mean change in number of lesions after 1 weeks, 9 weeks and 17 weeks post treatment as compared to baseline

Mean change in number of lesions as compared to baseline at Week 1, Week 9 and Week 17 for the intent-to-treat population

Fougera Pharmaceuticals Inc.

Icahn School of Medicine at Mount Sinai

Assistant Professor

There were no serious adverse events related to the study medication reported during the study. All subjects experienced mild to moderate local site reactions (eg, any symptom of erythema, edema, scaling, crusting, and erosion which were not collected separately) that were related to both cryotherapy and/or sinecatechins ointment. There were no subject discontinuations or dose interruptions.

Cryotherapy and then Sinecatechins 15% Ointment 1 week later.

Sinecatechins 15% Ointment: Following cryotherapy, half of the subjects randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy up to 16 weeks or until complete clearance.

Sinecatechins 15% Ointment & Cryotherapy

Cryotherapy standardized in all subjects and for all treated lesions: EGW lesions treated with 2 cycles, 5 seconds each, with a 5 second interval. All subjects treated with the same cryo-spray regimen.

Cryotherapy Alone

Sinecatechins 15% Ointment: Following cryotherapy, half of the subjects randomized to treatment with sinecatechins ointment twice daily starting one week after cryotherapy up to 16 weeks or until complete clearance.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Evaluate if Green Tea Can be Effective in Reducing the Progression of Prostate Cancer in Men on Close Monitoring	NCT04597359	Prostate Carcin...	Placebo Adminis... Quality-of-Life... Questionnaire A... Sinecatechins	21 Years -	Eastern Cooperative Oncology Group
Topical Green Tea Ointment in Treatment of Superficial Skin Cancer	NCT02029352	Carcinoma, Basa...	Sinecatechins 1... Placebo	18 Years -	Maastricht University Medical Center
Treatment of External Genital Warts With Cryotherapy and Sinecatechins 15% Ointment	NCT02147353	External Genita...	Sinecatechins 1... Cryotherapy alo...	18 Years -	Icahn School of Medicine at Mount Sinai

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