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CirrhosisPhase 1NCT03278925

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

A Phase 1 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Cirrhosis, run by National Cancer Institute (NCI) at 2 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 participants with cirrhosis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cirrhosis
What is being tested?
Biopsy, Biospecimen Collection and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
2 sitesin 2 countries
Study dates
9 Aug 2018to 31 Dec 2024
Phase
Phase 1
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

  • Participants with a clinical diagnosis of cirrhosis based on the investigators evaluation, confirmed by ANY ONE of the three following methods to define cirrhosis:
  • Established cirrhosis on liver biopsy (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] F4);
  • Ultrasound, CT or MRI findings consistent with cirrhosis; nodular appearing liver with or without evidence of portal hypertension
  • Transient elastography (FibroScan) with a result > 12.5 kPa 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
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  • Participant must be aged >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of Polyphenon E in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Platelets >= 75,000 / uL
  • Hemoglobin >= 8 g/dL
  • 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
  • Serum direct bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X upper normal level (UNL)
  • Albumin >= 3.0 mg/dL
  • International normalized ratio (INR) =< 1.3
  • Ascites absent
  • Encephalopathy absent
  • Only participants found to express high levels (immunohistochemistry [IHC] score 3 and above) of gamma-OHPdG (gamma-OHPdG-high HCC) in baseline or archival liver biopsy will be registered to receive Polyphenon E treatment
  • Participant is able to undergo radiographic evaluation with ultrasound, 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)

Who cannot join

  • Participant has confirmed HCC by ultrasound/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 registered 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
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  • 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); note that participants who are unable to tolerate intravenous contrast for CT scans should have MRIs or ultrasounds during the study instead of CT scans
  • 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 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

Puerto Rico1 site

  • University of Puerto Rico

    San Juan, 00936

Other trials in Puerto Rico

About this study

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

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 participants with cirrhosis. Higher levels of the molecule gamma-OHPdG may be found in participants 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.

Read the detailed description

PRIMARY OBJECTIVES:

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

  1. To collect Polyphenon E/EGCG pharmacokinetic data in participants 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 by liquid chromatography-mass spectrometry (LC-MS) assay from baseline to post-treatment.

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

EXPLORATORY OBJECTIVES:

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

II. To develop a 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.

III. To evaluate any hepatocellular carcinoma (HCC) development during the treatment.

OUTLINE: This is a dose-escalation study.

Participants 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. Patients undergo ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) at screening and on study, undergo collection of blood samples on study, and may undergo biopsy at screening and on study.

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

Conditions
Cirrhosis
Being tested
Biopsy, Biospecimen Collection, Computed Tomography, Defined Green Tea Catechin Extract, Laboratory Biomarker Analysis
Medical subject headings
Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Defined Green Tea Catechin ExtractDrug

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Pharmacological StudyOther

    Correlative studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • UltrasoundProcedure or surgery

    Undergo ultrasound

Study groups in NCT03278925
Study groupRoleWhat they receive
Prevention (defined green tea catechin extract)ExperimentalParticipants receive defined green tea catechin extract PO QD or BID for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo ultrasound, CT, or MRI at screening and on study, undergo collection of blood samples on study, and may undergo biopsy at screening and on study.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Defined Green Tea Catechin Extract; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Other: Pharmacological Study; Other: Questionnaire Administration; Procedure: Ultrasound

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of Polyphenon E

    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 criteria.

    Measured: Up to 4 weeks

  2. Change in gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) expression in cirrhotic liver

    Will be assessed by immunohistochemistry. Will use a nonparametric Wilcoxon test to compare the post-pre differences to zero.

    Measured: Baseline up to 24 weeks

Secondary outcomes (3)

  1. Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG

    Will use descriptive statistics.

    Measured: Up to 24 weeks

  2. Change in gamma-OHPdG

    Descriptive statistics (mean, range) will be used to summarize this continuous outcome by dose level. A nonparametric trend test will be used to examine whether there is a trend for greater reduction in gamma-OHPdG as the dose level increases.

    Measured: Baseline up to 24 weeks

  3. Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis

    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 participants.

    Measured: Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2017
  2. Study start9 Aug 2018
  3. Primary completion16 Jun 2023
  4. Study completion31 Dec 2024 (estimated)

Resources

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 1
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03278925
Sponsor's protocol ID
NCI-2017-01557
Other IDs
NCI-2017-01557, N01-CN-2012-00035, NCI 2016-08-02, NWU2016-08-02, N01CN00035, P30CA060553
Status last verified
Jul 2024
First submitted
11 Sep 2017
Last updated
2 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Cirrhosis, run by National Cancer Institute (NCI) at 2 sites in 2 countries.

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 20 inclusion and 19 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 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Puerto Rico. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Maximum tolerated dose of Polyphenon E (time frame: Up to 4 weeks). The study lists 2 primary outcomes in all. 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 NCT03278925.

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 2 Aug 2024.

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