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Non-Small Cell Lung CancerPhase 1NCT00707252

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

A Phase 1 study testing Polyphenon E and Tarceva in people with Non-Small Cell Lung Cancer, run by Louisiana State University Health Sciences Center Shreveport at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Polyphenon E and Tarceva
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
Jan 2008to Nov 2012
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

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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
  • Itraconazole
  • Ketoconazole
  • Nefazodone
  • Nelfinavir
  • Ritonavir
  • Saquinavir
  • Telithromycin
  • Troleandomycin
  • Voriconazole
  • Rifampicin
  • Rifabutin
  • Rifapentine
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • St John's Wort.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • LSUHSC-Shreveport, Feist-Weiller Cancer Center

    Shreveport, Louisiana, 71103

Other trials in United States

About this study

Official title: Phase I/II Study of Polyphenon E in Addition to Erlotinib in Advanced Non Small Cell Lung Cancer

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.

Read the detailed description

To evaluate the short term effects of Polyphenon E administered alone and in combination with erlotinib to patients with advanced Stage IIIB or IV Non Small Cell Lung Cancer (NSCLC) that has progressed after first line chemotherapy. We will do a Phase I dose escalation study with Polyphenon E and a fixed dose of erlotinib to evaluate for any significant adverse events related to the combination.

Once the maximum tolerated dose (MTD) of Polyphenon E has been established the Phase II trial will be embarked upon using this dose in combination with erlotinib. In both the Phase I and Phase II parts the agents will administered until time of progression or unacceptable side effects occur.

The primary end point of the Phase I part is establishing the safety, tolerability and MTD of Polyphenon E in combination with erlotinib given at 150mg per day.

The Primary endpoint of the Phase II part that will be studied is Response rate (RR) to the combination. Progression free survival (PFS), Overall Survival (OS) and the safety and tolerability of Polyphenon E in addition to erlotinib in this subject population and setting will be assessed as secondary objectives.

Changes in serum markers related to progression of cancer will also be studied as part of the Phase I and phase II study. The effect of Polyphenon E with or without erlotinib on the serum levels of circulating c-met RNA, Interleukin-8 (Il-8), Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) will be studied as secondary objectives. Epidermal Growth Factor Receptor (EGFR) expression of the initial tumor tissue and testing for EGFR mutations in the tumor tissue and serum DNA and evaluation of "KIRSTEN RAT SARCOMA VIRAL ONCOGENE HOMOLOG" (KRAS) mutations with correlation of these results with treatment outcome will also be undertaken as secondary objectives in both the Phase I and II parts.

1.1 Determine the safety, tolerability and MTD of Polyphenon E given in combination with erlotinib. Polyphenon E dose-escalation from 200, 400 and 800mg/day will be performed to evaluate for the MTD when used together with erlotinib 150mg/d.

1.2 Determine the effects of Polyphenon E in addition to erlotinib on response rate, progression free survival and overall survival

1.3 Determine the effects of Polyphenon E on circulating serum C-met messenger RNA

1.4 Determine the effects of Polyphenon E on serum HGF levels

1.5 Determine the effects of Polyphenon E on serum Il-8 levels

1.6 Determine the effects of Polyphenon E on serum VEGF levels 1.7 Determine the safety and tolerability of Polyphenon E in addition to erlotinib in this subject population

1.8 Determine the possible correlation between EGFR expression on original tumor tissue, EGFR mutations in tumor tissue and serum DNA and the presence of KRAS mutations with the treatment response and outcome.

This study was intended to be a Phase I/II study. This study never moved into the Phase II portion of the study. The sponsor stopped supplying Polyphenon E and there was not enough of a supply in-house to continue with Phase II.

Being tested
Polyphenon E, Tarceva
Keywords
Non-small cell lung cancer, Erlotinib, Polyphenon E, Tarceva, Advanced Non-small Cell Lung Cancer Stage IIIb or IV
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • Polyphenon EDrug

    Also called "Polyphenon extract, Green Tea"

    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.

  • TarcevaDrug

    Also called (Erlotinib)

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

Study groups in NCT00707252
Study groupRoleWhat they receive
Phase I/IIExperimentalPhase 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.
Receives: Drug: Polyphenon E; Drug: Tarceva

What is being measured

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

  1. 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.

    Measured: 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.

  2. 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.

    Measured: 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.

  3. 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.

    Measured: 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)

  1. Phase I: 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.

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

  2. Phase 1: Progression Free Survival

    Progression- Free Survival:

    From date of registration to date of first observation of progressive disease, death due to any cause or symptomatic deterioration.

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

  3. Phase 2: Progression Free Survival

    From date of registration to date of first observation of progressive disease, death due to any cause or symptomatic deterioration.

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

  4. Phase 2: Overall Survival

    Time from registration to death of any cause measured in months.

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

  5. 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.

    To analyze signaling pathway activity western blot analysis will be performed using antibodies that recognize serum interleukin-8 (IL-8), VEGF and HGF levels. The level of circulating C-met RNA will be measured using Real Time Polymerase Chain Reaction (RT-PCR).

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

  6. Phase 2: Correlation of KRAS mutations (in exons 2 and 3) in the original tumor tissue with treatment response and outcome.

    Clinical assay for detecting mutations in KRAS (direct sequencing).

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

Timeline

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

  1. First posted30 Jun 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionNov 2012
  4. Study completionNov 2012

Why it stopped: Phase II not initiated due to cancellation of supply of Poly E by collaborator.

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00707252
Sponsor's protocol ID
H06-128
Status last verified
Apr 2015
First submitted
26 Jun 2008
Last updated
21 Apr 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Polyphenon E and Tarceva in people with Non-Small Cell Lung Cancer, run by Louisiana State University Health Sciences Center Shreveport at 1 site in United States.

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 11 inclusion and 31 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: stopped early, as of the sponsor's last update on 21 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

The study was stopped early (reason given: Phase II not initiated due to cancellation of supply of Poly E by collaborator.). 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?

Phase 1: Number of Participants with Adverse Events. (time frame: 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.). The study lists 3 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 NCT00707252.

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 21 Apr 2015.

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