Study of Polyphenon E in Addition to Erlotinib in Advanced Non Small Cell Lung Cancer

NCT00707252 | Terminated Phase 1 DMC

• 1 other identifier: H06-128
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to study if the addition of the green tea extract, Polyphenon E, to Erlotinib is safe and if it has potential to improve outcomes in second line therapy for Advanced Stage IIIb/IV Non-small cell lung cancer.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-small cell lung cancer; Erlotinib; Polyphenon E; Tarceva; Advanced Non-small Cell Lung Cancer Stage IIIb or IV

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants with Adverse Events.

  Toxicity evaluation of all adverse events monitored by physical exam, weight, vital signs, Complete Blood Count (CBC), Complete Metabolic Panel (CMP), coagulation panel and Computed Tomography (CT) scans of the chest, abdomen and pelvis, CT/Magnetic Resonance Imaging (MRI) of the head.

  At Screening and every week for first 4 weeks and then week 6, 8 and then every 4 weeks in Phase I study. Liver function tests will be monitored at least every 4 weeks as applicable. The patients will be followed up to 2 years on average.

• Phase 1: Maximum Tolerated Dose

  Dose-Limiting Toxicity (DLT) is defined as two or more events with grade 3 toxicity or a single event with grade 4-5 toxicity possibly or probably related to the study medications at a specific dose of Polyphenon E.

  Day 1 of Phase I until progression, death or intolerable side effects would occur. The patients will be followed up to 2 years on average.

• Phase 2: Response Rate

  Response Rate defined as Complete (CR) + Partial Response (PR) using RECIST criteria. Complete response (CR): Complete disappearance of all measurable and non-measurable disease, no new lesions, no disease related symptoms, and normalization of markers and other abnormal lab values. All disease must be assessed using the same technique as baseline. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.

  Start of Phase 2 to until progression, death or intolerable side effects occur. The patients will be followed up to 2 years on average.

Secondary Outcomes (6)

• Phase I: Response rate

  From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.

• Phase 1: Progression Free Survival

  From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.

• Phase 2: Progression Free Survival

  From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.

• Phase 2: Overall Survival

  From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.

• Phase 2: Correlation between level of EGFR expression on the original tumor tissue and the presence of EGFR mutations in exons 18, 19 and 21 in serum DNA and original tumor tissue with the treatment response and outcome.

  Pre-study until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.

Study Arms (1)

Phase I/II

EXPERIMENTAL

Phase I: Polyphenon E + Erlotinib - Polyphenon E 200, 400 and 800 mg/day dose levels evaluated in a step-wise manner with Erlotinib 150 mg/day to establish Maximum Tolerated Dose (MTD) of Polyphenon E. Phase II consists of MTD of Polyphenon E established in Phase I, administered alone for two weeks and thereafter together with Erlotinib 150 mg/day.

Drug: Polyphenon E; Drug: Tarceva

Interventions

Polyphenon E DRUG

Patients will be assigned to 3 sequential cohorts of three different dose levels of Polyphenon E (providing 200, 400 and 800mg of Polyphenon E given once daily) in a step-wise manner.

Also known as: "Polyphenon extract, Green Tea"

Phase I/II

Tarceva DRUG

All patients will also receive Erlotinib 150mg po/day from Day 1.

Also known as: (Erlotinib)

Phase I/II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy proven NSCLC
• Stage IIIB or IV measurable disease burden after routine staging work up.
• Documented disease progression after first or second line chemotherapy. This will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST)
• Ability to give informed consent and willingness to adhere to study protocol
• Ability to take oral medication
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status between 0-2
• Adequate hematological, hepatic and renal function defined as below:
• granulocyte count \> 1500/mm3, platelet count \> 100.000/mm3, serum creatinine \< 1.5; bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) at or below institutional upper limit of normal (IULN). All lab values should be obtained within 14 days of registration.
• Patients have to have recovered from any toxic effects of prior chemotherapy or radiation therapy to a Grade 1 or less (except from alopecia). Enrollment should occur no less than 28 days after completion of prior therapy.
• Ability to comply with the use of contraceptive measures starting 1 week before and ending 2 weeks after the last dose of study drug.

You may not qualify if:

• Liver or kidney problems that would interfere with metabolism of study drug. This includes any preexisting elevation of AST, ALT, ALP or bilirubin.
• Any condition that would hamper informed consent or ability to comply with the study protocol
• Participation in another research study in the last three months
• Known malignancy at any site other than NSCLC
• Recent consumption of green tea (5 or more cups per day within one week of study enrollment)
• Significant history of cardiac disease, e.g. uncontrolled hypertension, unstable angina, congestive-heart failure, myocardial infarction within the last six months or ventricular arrhythmias requiring medication.
• Presence of metastatic brain lesions
• Documented history of bleeding diathesis
• Need to be on therapeutic anticoagulation
• Pregnant and lactating women
• Patients with a known seizure disorder who are taking Phenytoin, Carbamazepine or Phenobarbital
• Patients taking medications known to interfere with erlotinib metabolism as listed below.
• Atazanavir
• Clarithromycin
• Indinavir

Sponsors & Collaborators

• Louisiana State University Health Sciences Center Shreveport: lead
• Polyphenon E International,Inc.: collaborator

Study Sites (1)

LSUHSC-Shreveport, Feist-Weiller Cancer Center

Shreveport, Louisiana, 71103, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

polyphenon E; Tea; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Glenn M Mills, MD

  LSU Health Sciences Center - Shreveport

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: June 30, 2008
• Study Start: January 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 21, 2015

Record last verified: 2015-04

Locations

US (1)