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Trial record 21 of 84 for:    catechin

Defined Green Tea Catechin Extract in Preventing Liver Cancer in Patients With Cirrhosis

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ClinicalTrials.gov Identifier: NCT03278925
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I trial studies the side effects and best dose of defined green tea catechin extract and to see how well it works in preventing liver cancer in patients with cirrhosis. Higher levels of the molecule gamma-OHPdG may be found in patients with cirrhosis, which may mean a higher risk of the development of liver cancer. Defined green tea catechin extract may work better to lower levels of gamma-OHPdG and prevent the development of liver cancer.

Condition or disease Intervention/treatment Phase
Cirrhosis Drug: Defined Green Tea Catechin Extract Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Questionnaire Administration Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish maximum tolerated dose (MTD) and to collect safety data of defined green tea catechin extract (Polyphenon E/epigallocatechin gallate [EGCG]) treatment in patients with cirrhosis.

II. To determine the effects of Polyphenon E/EGCG treatment on the suppression of gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) levels in cirrhotic liver.

SECONDARY OBJECTIVES:

I. To collect Polyphenon E/EGCG pharmacokinetic data in patients with cirrhosis.

II. To study the correlation between gamma-OHPdG levels and mutation frequency and deoxyribonucleic acid (DNA) damage spectrum in the p53 and beta-catenin genes in cirrhotic liver tissue.

III. To estimate the fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG.

EXPLORATORY OBJECTIVES:

I. To assess the effects of Polyphenon E/EGCG on the grade of cirrhosis as measured by FibroScan and Fibrosis-4 (FIB-4) score.

II. To develop a liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting urinary and blood gamma-OHPdG, to correlate with liver gamma-OHPdG levels.

OUTLINE: This is a dose-escalation study.

Patients receive defined green tea catechin extract orally (PO) once daily (QD) or twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study intervention, patients are followed up at 28 days.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase I Single-arm, Multicenter Pilot Study Aimed at Validating γ-OHPdG as a Biomarker and Testing the Effects of Polyphenon E on Its Levels in Patients With Cirrhosis
Actual Study Start Date : August 9, 2018
Estimated Primary Completion Date : January 15, 2020
Estimated Study Completion Date : January 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
Experimental: Prevention (defined green tea catechin extract)
Patients receive defined green tea catechin extract PO QD or BID for 24 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Defined Green Tea Catechin Extract
Given PO

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Maximum tolerated dose of Polyphenon E [ Time Frame: Up to 4 weeks ]
    Will be defined as the dose at which =< 1 subjects out of 6 experiences a grade 3 or higher toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) criteria.

  2. Change in gamma-OHPdG expression in cirrhotic liver [ Time Frame: Baseline up to 24 weeks ]
    Will be assessed by immunohistochemistry (IHC). Will use a nonparametric Wilcoxon test to compare the post-pre differences to zero.


Secondary Outcome Measures :
  1. Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG [ Time Frame: Up to 24 weeks ]
    Will use descriptive statistics.

  2. Change in mutation frequency in cirrhotic liver tissue [ Time Frame: Baseline up to 24 weeks ]
    The mutation frequencies will be correlated with the change of gamma-OHPdG level in liver tissue. Will use graphics and a nonparametric correlation measure such as Spearman's correlation.

  3. Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis [ Time Frame: Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1 ]
    Clearance of Polyphenon E will be compared among cirrhotic liver patients in this study and results from this population will be compared with non-cirrhotic historical control patients.


Other Outcome Measures:
  1. Grade of cirrhosis [ Time Frame: Up to 24 weeks ]
    Will be assessed by FibroScan and Fibrosis-4 score.

  2. Liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting gamma-OHPdG [ Time Frame: Up to 24 weeks ]
    The research urine samples at screen 2 and research blood samples collected at visit 1, visit 2, and Visit 3 will be used to develop a non-invasive LC-MS and/or ELISA-based method to quantify gamma-OHPdG in urine and blood samples of collected from trial patients. Descriptive statistics (n; minimum [min]; maximum [max]; mean; median; standard deviation [SD] for continuous variables; and n, frequency for categorical variables) will be used to summarize patient demographics. Patient safety data will be tabulated according to the symptom and grade. Estimates will be presented with their 95% confidence intervals.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with a clinical diagnosis of cirrhosis based on the investigator's evaluation, confirmed by any one of following methods to define cirrhosis:

    • Established cirrhosis on liver biopsy (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] F4);
    • Computed tomography (CT) or magnetic resonance imaging (MRI) findings consistent with cirrhosis; nodular appearing liver with or without evidence of portal hypertension
    • Transient elastography (FibroScan) with a result > 12.5 kPa
    • FibroScan score > 0.75 and aspartate aminotransferase (AST) to platelet ratio index (APRI) > 2
    • Etiology of cirrhosis will not be considered in determining inclusion in the study
  • Participant is able and willing to comply with study procedures, and signed and dated informed consent is obtained
  • Participant agrees to consume no more than 2 cups of green tea per day and refrain from taking supplements or foods labeled as containing green tea
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Platelets >= 75,000 / uL (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Hemoglobin >= 8 g/dL (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Serum creatinine OR measured or calculated creatinine clearance within normal institutional limits; glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) within normal institutional limits as adjusted for age and sex (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Serum total bilirubin within normal institutional limits (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • AST (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X upper normal level (UNL) (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Albumin >= 3.5 mg/dL (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • International normalized ratio (INR) or prothrombin time (PT) within normal institutional limits (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Activated partial thromboplastin time (aPTT) within normal institutional limits (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Ascites absent (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Encephalopathy absent (obtained within 4 weeks [unless noted otherwise] prior to beginning polyphenon E)
  • Only participants found to express high levels (immunohistochemistry [IHC] score 3 and above) of gamma-OHPdG (gamma-OHPdG-high hepatocellular carcinoma [HCC]) in baseline liver biopsy will be enrolled to receive Polyphenon E treatment
  • Screening visit 2 must occur within 8 weeks prior to administration of the first dose of Polyphenon E
  • Participant is able to undergo radiographic evaluation with CT or MRI
  • The effects of Polyphenon E on the developing human fetus at the recommended therapeutic dose are unknown; for this reason,women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence); contraception must be used prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (if a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required)

Exclusion Criteria:

  • Participant has confirmed HCC by CT/MRI; participants who have previously had HCC but have been treated and have been recurrence free for 5 years are eligible
  • Participant has or has had other cancer(s) within 3 years of study; however, in situ breast, in situ cervical, and basal cell/squamous cell skin cancers are allowed; participant with active, other cancer that requires systemic therapy will be excluded from this study; participant with early stage cancer that requires local therapy, such as cervical ablation for early stage cervical cancer, are allowed to be enrolled in the study and are allowed to receive local therapy
  • Inability to swallow capsules
  • Participant has a known diagnosis of mental incapacitation that may affect their ability to consent and be compliant with the protocol
  • Participant has ever experienced one or more hepatic decompensation events or a history of decompensated liver disease as listed below:

    • Clinical ascites
    • Variceal bleeding documented by endoscopy
    • Spontaneous bacterial peritonitis documented by positive culture
    • Hepatic encephalopathy
    • Hepatorenal syndrome (type 1 or 2)
    • Porto-pulmonary hypertension
    • Hepato-pulmonary hypertension
    • Any liver-related event which led to a hospitalization or a grade 4 event
  • Participant has an underlying predisposition to gastrointestinal (GI) or rectal bleeding are considered ineligible for study participation
  • History of allergic reactions attributed to compounds of similar chemical composition to Polyphenon E (or green tea), or intravenous contrast that is required for CT scan
  • Participant is receiving any other investigational agents
  • Participants have taken supplements or foods that are labelled as containing green tea for 8 weeks before start of treatment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; hepatitis b virus (HBV) and hepatitis C virus (HCV) infections are allowed
  • Green tea has been consumed by humans for thousands of years and teratogenic or abortifacient effects have not been reported; however, subjects in this study will take high doses of Polyphenon E; the teratogenic or abortifacient effects of high dose Polyphenon E is unknown; therefore pregnant women are excluded from this study; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with Polyphenon E, breastfeeding should be discontinued if the mother is treated with this study agent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03278925


Locations
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United States, District of Columbia
MedStar Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Contact: Aiwu R. He    202-444-2223    arh29@georgetown.edu   
Principal Investigator: Aiwu R. He         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Aiwu R He Northwestern University

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03278925     History of Changes
Other Study ID Numbers: NCI-2017-01557
NCI-2017-01557 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00035
NCI 2016-08-02 ( Other Identifier: Northwestern University )
NWU2016-08-02 ( Other Identifier: DCP )
N01CN00035 ( U.S. NIH Grant/Contract )
P30CA060553 ( U.S. NIH Grant/Contract )
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fibrosis
Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Neuroprotective Agents