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Study Summary
No. 2004-0907:.......Cancer Prevention; Esophageal; Gastrointestinal......Robert S. Bresalier......Gastroenterology/Hepatology and Nutrition
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Study Summary Title
Study Summary
Number:
2004-0907
Study Title:Phase Ib Randomized, DOUBLE-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus
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Physician New Patient Referral
Name:Robert S. BresalierPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastroenterology/Hepatology and NutritionReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-5073
Contact us about clinical trials
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General Information
Disease Group:Cancer Prevention
Esophageal
Gastrointestinal
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
Baseline Testing Pre-Study Visit
Research-related EGD (pre-intervention)
Month 1 [wks 1 and 3]
Months 2 , 4 and 5 [wk 1]
Month 3 [wk 1]
Evaluations at Completion of Intervention/ Month 6
Research-related EGD at month 6 (post-intervention)
Months 9 and 12
Treatment
Agents:
Green TeaHome Care:N/A
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to test the safety of Polyphenon E
(Poly E) at different dose levels. Researchers also want to find out what
effects, good and bad, it may have on you and your risk for esophagus cancer.
Esophagus cancer is an increased risk associated with Barret's Esophagus.
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Study Objectives / Outcomes
Primary Objectives:
The primary objective of this study is to demonstrate the safety of using Polyphenon E (Green Tea extract) over a six-month period in the management of patients with Barrett's Esophagus with or without low-grade dysplasia.

Secondary Objectives:
Secondary objectives are to investigate the dose-related biologic effects and pharmacodynamic properties of Poly E:
1. determine the efficacy of Poly E in inhibiting phosphorylation of EGFR or Her-2 or akt in esophageal mucosa;
2. determine the pharmacodynamic profile of Poly E constituents in esophageal tissue during and after 6 months of therapy using HPLC and GC-MS;
3. evaluate the efficacy of Poly E in reducing or stabilizing metaplasia and dysplasia of esophageal Barrett's mucosa using visual endoscopic measurements and histological analysis.
4. determine the efficacy of Poly E in modulating surrogate biomarkers in esophageal mucosa – degrees of tetraploidy and aneuploidy; expression of cyclin D1, COX-2, EGFR, Her-2, akt, and Ki-67; LOH at 9p and 17p; apoptotic index;
5. determine the efficacy of Poly E in inhibiting methylation of p16;
6. and determine the efficacy of Poly E in modulating eicosanoid levels and lipoxygenase profiles in esophageal mucosa.

The proposed trial will help to validate the safety demonstrated in the initial studies.
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Study Status Information
Study Activation / Registration Date:07/18/2006
IRB Review and Approval Date:01/05/2005
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:55
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Histologically-confirmed diagnosis of Barrett's metaplasia within 12 months prior to trial entry. Note: The presence of LGD may be subject to disagreement between pathologists. This will not affect trial entry, since patients with or without LGD are eligible to participate. All cases in which there is disagreement regarding the presence of LGD will be reviewed by a third pathologist for histological classification prior to the efficacy analysis.

2) Cases of short-segment (less than or equal to 3cm) Barrett's esophagus must be large enough to allow adequate sampling of tissue without completely resecting the metaplasia.

3) Age greater than or equal to 18 years.

4) ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%)

5) Participants must have normal organ and marrow function as defined below: Leukocytes greater than or equal to 3,000/UL; Absolute neutrophil count greater than or equal to 1,500/UL; Platelets greater than or equal to 100,000/UL; Total bilirubin within normal institutional limits; AST (SGOT)/ALT (SGPT) less than or equal to institutional ULN; Creatinine within normal institutional limits. Alkaline phosphatase less than or equal to the institutional ULN.

6) Willingness to abstain from all tea consumption while on the study drug.

7) Willingness to record intake of caffeine-containing foods and medications while on the study. A significant portion of caffeine intake occurs from "hidden" sources, including medications and foods. Study subjects will be provided a list of permissible medications, beverages and foods which contain caffeine.

8) Participants may continue therapy with proton pump inhibitors, nonsteroidal anti-inflammatory agents, and celecoxib or rofecoxib.

9) Pregnancy testing to within 2 weeks prior to randomization. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. If a female participant does become pregnant while on study, she will be removed from the study.

10) Willingness to comply with all treatment and follow-up procedures.

11) Willingness to wait at least one month since last endoscopic evaluation.

12) Ability to understand and willingness to sign a written informed consent document.

13) Inclusion of Women and Minorities. Both men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:1) Histologically confirmed high-grade dysplasia.

2) Histologically confirmed diagnosis of invasive carcinoma of the esophagus.

3) Prior endoscopic therapy for Barrett's esophagus, including mucosal ablation, resection and esophagectomy, and photodynamic therapy.

4) History of esophageal strictures with moderate-to-severe dysphagia or odynophagia that may interfere with ingestion/swallowing of the study drug. Trial participation will be determined by the study investigator after consideration of other factors including severity of dysphagia and odynophagia, necessity for treatment of strictures, and nutritional status.

5) History of allergic reactions attributed to compounds of similar chemical or biologic composition to Poly E.

6) Participants may not be receiving any other investigational agents within 30 days prior to randomization or during the study.

7) Use of medications, herbs, and vitamin and mineral supplements that contain tea compounds should not be taken while participating in the study and on study drug and for 30 days prior to trial entry. If patients are consuming any of these items and would like to participate in this study, then a 30-day voluntary washout will be required.

8) Uncontrolled or significant co-morbid illness including, but not limited to, active or serious infection requiring intravenous antibiotics; symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia; active gastrointestinal bleeding; predisposing condition to gastrointestinal bleeding (including but not limited to gastritis, diverticulitis, colitis, and hemorrhoids); active malignancy diagnosed or treated within 5 years, except for squamous cell carcinoma of the skin, basal cell carcinoma of the skin, carcinoma in situ,

9) Continued from # 8. Stages Ia or Ib invasive squamous cell carcinoma of the cervix treated by surgery and/or radiation therapy, Stage Ia Grade 1 adenomcarcinoma of the endometrium treated with surgery; patients receiving active chemotherapy or radiation; or psychiatric illness/social situations that would limit compliance with study requirements.

10) Participants will not take aspirin, aspirin-containing substances, coumadin (warfarin), heparin, or iron for 5 days before each endoscopy.

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Links
Registration Number: NCT00233935
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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