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Polyphenon E in Treating Patients With High-Risk of Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01606124
Recruitment Status : Terminated (pending expiration of the supply of study agent.)
First Posted : May 25, 2012
Results First Posted : September 28, 2017
Last Update Posted : October 27, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
This phase II trial studies how well Polyphenon E works in treating patients with high-risk of colorectal cancer. Polyphenon E contains ingredients that may prevent or slow colorectal cancer.

Condition or disease Intervention/treatment Phase
Advanced Colorectal Adenomas Adenocarcinoma of the Colon Stage I Colon Cancer Stage II Colon Cancer Stage III Colon Cancer Drug: defined green tea catechin extract Other: placebo Other: questionnaire administration Other: laboratory biomarker analysis Phase 2

Detailed Description:
PRIMARY OBJECTIVES: I. To determine whether POLYE (Polyphenon E) treatment is associated with a significant percent decrease in the number of rectal Aberrant Crypt Foci (ACF) (% change in ACF) identified during the pre-intervention and post-intervention chromoendoscopy exams. SECONDARY OBJECTIVES: I. To determine the relative tolerability and safety of treatment with 2 capsules of POLYE taken twice a day by mouth (Note: each capsule of Polyphenon E contains approximately 200 mg of epigallocatechin gallate (EGCG) versus placebo administered for 6 months. TERTIARY OBJECTIVES: I. To determine the effect of the study drug vs. placebo on EGCG levels in plasma and to correlate EGCG levels with drug compliance and toxicity. II. To characterize ACF based on four criteria and correlate such characterizations with the intervention (vs placebo), as well as exploring the natural history of ACF over 6 months in persons at high risk for colorectal cancer randomized to placebo. III. To correlate the 6-month measurements of ACF size (e.g., number of crypts/ACF), number, morphology, and histopathology with the adenoma recurrence data at the next surveillance endoscopy. IV. To assess caffeine and black tea consumption via a Beverage Consumption Questionnaire and correlate with study endpoints. V. To assess the effects of POLYE versus placebo on a focused panel of tissue biomarkers using re- and post-intervention biopsy samples obtained from ACF and normal-appearing rectal mucosa. Residual tissue will be stored for further analysis. VI. To study the association of clinical (toxicity and/or ACF response or activity) with the pharmacokinetic parameters, and/or biologic (pharmacodynamic) results. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive Polyphenon E orally (PO) twice daily (BID). ARM II: Patients receive placebo PO BID. Courses in both arms repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Polyphenon E vs.Placebo in Patients at High Risk of Recurrent Colonic Neoplasia
Study Start Date : June 2012
Actual Primary Completion Date : May 21, 2015
Actual Study Completion Date : May 21, 2015

Arm Intervention/treatment
Experimental: Arm I (Green Tea Catechin Extract)
Patients receive Polyphenon E PO BID. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
Drug: defined green tea catechin extract
Given PO
Other Name: Polyphenon E

Other: questionnaire administration
Ancillary studies

Other: laboratory biomarker analysis
Correlative studies

Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
Other: placebo
Given PO
Other Name: PLCB

Other: questionnaire administration
Ancillary studies

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Percent Change in Rectal ACF, Pre- and Post Intervention at 6 Months [ Time Frame: 6 months ]
    The primary endpoint is based on a modified intent-to-treat procedure which includes all patients with baseline and 6-month ACF data. The percent change in rectal ACF (≤ 15 cm from the anal verge) for each patient is calculated as their Pre-Registration number of rectal ACF minus the number of rectal ACF present at the 6-month post-intervention exam, divided by the number of rectal ACF present at Pre-Registration times 100.

Secondary Outcome Measures :
  1. Tolerability as Estimated Using the Percent Dose of Treatment Received at 6 Months [ Time Frame: 6 months ]
    Tolerability as estimated using the percent dose of treatment received for each patient by dividing the total dose received by the targeted (i.e., protocol specified) total dose.

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Current or prior advanced adenomas. Participants with advanced adenomas are defined as participants who have polyps >= 1 cm, who have tubulovillous adenomas (25-75 percent villous features), who have villous adenomas (>75 percent villous), or who have severe dysplasia
  • Prior curatively resected Tumor, Node, Metastasis (TNM) stage II and III colon cancer >= 3 years out from treatment by surgery with/without adjuvant chemotherapy; NOTE: patients with stage I (T1,2 N0) colon cancer treated by endoscopic or surgical therapy are eligible at anytime after such therapy; patients with prior stage IV disease must be >= 5 years status post surgical resection of all metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to discontinue regular usage of calcium supplements; Exception: multi-vitamin; regular use defined as a frequency of 7 consecutive days for > 3 weeks
  • Willingness to provide mandatory tissue and blood for protocol specified research; residual tissue and/or blood may be used for future research Negative pregnancy test =< 7 days prior to registration/randomization
  • Hemoglobin (Hgb) >= 12.0 g/dL (women), >= 13.5 g/dL (men) at Mayo Clinic or within normal limits at an outside laboratory
  • Platelet count >= 100,000/ul
  • White blood cells (WBC) >= 3,000/ul
  • Alanine aminotransferase (ALT) within institutional limits of normal
  • Alkaline phosphatase within institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) within institutional limits of normal
  • Total bilirubin within institutional limits of normal
  • Serum calcium =< institutional ULN
  • Serum creatinine =< 1.5 x institutional ULN
  • >= 5 rectal ACF detected by chromoendoscopy =< 45 days prior to registration/randomization
  • Endoscopy =< 45 days prior to registration/randomization; Note: All adenomas or polyps will be removed according to institutional standards of care, and the cecum must visualized; this may be done at the same time as the chromoendoscopy

Exclusion Criteria:

  • Any history of rectal cancer; Exception: transanal excision without radiation
  • Known diagnosis of colon heritable cancer syndrome (Familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) or inflammatory bowel disease (Crohn's disease, ulcerative colitis)
  • Inability to swallow capsules
  • Bleeding diathesis
  • Any invasive malignancy =< 5 years prior to pre-registration;

    • Exceptions:
    • patients with nonmelanoma skin cancers that were treated with simple excisional biopsy or stage I (T1,2 N0)
    • colon cancer treated by endoscopic therapy or surgery are eligible
  • History of gastroduodenal ulcers documented =< 1 year
  • Known inability to participate in the scheduled follow-up tests
  • Significant medical or psychiatric problems which would make the participant a poor protocol candidate, in the opinion of the treating physician
  • Total colectomy
  • Colostomy
  • History of pelvic or rectal radiation therapy
  • History of liver disease
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
  • Concomitant corticosteroids or anticoagulants needed on a regular or predictable intermittent basis
  • Use of non-study investigational agent(s) =< 3 months prior to preregistration
  • Chemotherapy =< 6 months prior to pre-registration; Note: Topical chemotherapy will be assessed on a case-by-case basis
  • Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception Note: This study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown
  • Over-the-counter green tea or green tea extract use =< 6 weeks prior to pre-registration; consumption of over the counter green tea extracts or drinking of green tea is not permitted during the treatment portion of this trial
  • Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) =< 6 weeks prior to pre-registration; regular use of NSAIDs is defined as a frequency of 7 consecutive days (1 week) for > 3 weeks; participant must abstain from regular use of NSAIDs for the duration of the study; Exception: low dose aspirin (81 mg) for those participants who are chronic users of aspirin prior to the beginning of the study
  • Use of non-study investigational agents while on study

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 identifier (NCT number): NCT01606124

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United States, Illinois
University of Illinois
Chicago, Illinois, United States, 60612
Hines Veteran's Administration Hospital
Hines, Illinois, United States, 60612
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
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Principal Investigator: Frank Sinicrope Mayo Clinic
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Responsible Party: Mayo Clinic Identifier: NCT01606124    
Obsolete Identifiers: NCT01974960
Other Study ID Numbers: MC084C
NCI-2012-00058 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: May 25, 2012    Key Record Dates
Results First Posted: September 28, 2017
Last Update Posted: October 27, 2017
Last Verified: May 2017
Additional relevant MeSH terms:
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Colonic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Epigallocatechin gallate
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Neuroprotective Agents