Cancer of Head and NeckPhase 1NCT01116336
Phase I Chemoprevention Trial With Green Tea Polyphenon E & Erlotinib in Patients With Premalignant Lesions of the Head & Neck
A Phase 1 study testing Erlotinib and Green Tea Polyphenon E in people with Cancer of Head and Neck and Neoplasms, Head and Neck, run by Emory University at 3 sites in United States.
Trial summary
The purpose of this study is to test the preventive effects of a combination of drugs: polyphenon E (PPE) derived from green tea extracts, and erlotinib. Because this combination of drugs has not been tested in humans before for the prevention of cancer, it is not clear which dose of each agent will be optimal in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Head and Neck, Neoplasms, Head and Neck
- What is being tested?
- Erlotinib and Green Tea Polyphenon E
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2010to May 2018
- 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 premalignant lesions (mild dysplasia, moderate dysplasia, severe dysplasia, or carcinoma in situ) of the head and neck, as confirmed by biopsy within the 4 months prior to study entry or a treated primary T1N0 or T2N0 squamous cell carcinoma will be eligible.
- For patients with T1N0 or T2N0 treated squamous cell carcinoma, they must have been free of disease for a minimum period of 8 weeks, up to a maximum of 3 years following completion of surgery and/or radiotherapy.
- Eligible tumor and premalignant lesion sites include oral cavity (buccal mucosal, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, larynx (glottis, supraglottis, subglottis, epiglottis), hypopharynx paranasal sinus and nasal cavity.
- Patients with a treated tumor 1-node 0 (T1N0) or tumor 2-node 0 (T2N0) squamous cell carcinoma may have oral premalignant lesions (i.e., hyperplasia, dysplasia, carcinoma in situ) at the time of study entry (provided their Stage I or II disease has been definitively treated).
- Lesion sites include oral cavity (buccal mucosa, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, hypopharynx,larynx (glottis, supraglottis, subglottis, epiglottis), nasopharynx and paranasal sinuses.
- Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1.
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- No medical contraindications for flexible laryngoscopy using topical anesthesia, and in the setting of a contraindication to topical anesthesia, general anesthesia may not be used as a substitute.
- General anesthesia, if indicated, is acceptable in patients whose lesions would require general anesthesia for laryngoscopy and biopsy according to routine standard of care.
- Blood counts: total neutrophil count > 1,500/mm³; platelet count > 100,000/mm³.
- Adequate liver function:
- Total bilirubin level ≤ 1.5 times upper limit normal (ULN)
- Albumin > 2.5 g/dl
- Alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
- Adequate renal function: serum creatinine < 1.5 mg/dl.
- Hemoglobin level ≥ 11gm/dl (age adjusted if appropriate) provided by the reference laboratory performing the test.
- Patients not taking warfarin must have prothrombin time (PT)/partial thromboplastin time (PTT) levels ≤ 1.5 times the upper limit of normal provided by the reference laboratory performing the test.
- Adequate pulmonary function: forced expiratory volume at one second (FEV1) and forced vital capacity (FVC) at least 60% predicted value by spirometry.
- Signed written informed consent.
- The effects of polyphenon E on the developing human fetus at the recommended dose are unknown. For this reason and because polyphenon E may be teratogenic, 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
- Women of child-bearing potential must also have a negative urine pregnancy test (β-HCG) within 72 hours of receiving treatment.
- Must be able to swallow the oral doses of erlotinib and PPE.
- Must be willing to abstain from drinking green tea or taking supplements containing green tea or green tea compounds, for the duration of the investigation and for 30 days prior to study entry.
- Please note that patients with a treated T1N0 or T2N0 squamous carcinoma and who do not have a pre-malignant measurable lesion at the time of study entry will not be subjected to a biopsy but will have cytobrush samples taken as specified in the protocol.
Who cannot join
- Because no dosing or adverse event data are currently available on the use of Polyphenon E in participants < 18 years of age, children are excluded from this study.
- Participants with hyperplasia, in absence of dysplasia or carcinoma in situ, will be excluded because there is possibly no benefit.
- Participants with acute intercurrent illness or those who had surgery within the preceding 4 weeks unless they have fully recovered.
- History of previous malignancies unless the cancer was stage I or II and rendered free of disease more than 1 year.
- Participants who are pregnant or breast feeding. Pregnant women are excluded from this study because Polyphenon E is an investigational agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Polyphenon E, breastfeeding should be discontinued if the mother is treated with Polyphenon E.
- Not practicing adequate contraception if the participants are of child bearing potential.
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- Uncontrolled intercurrent illness including, but not limited to, severe active infection, symptomatic congestive heart failure, myocardial infarction within the past six months, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are excluded.
- Documented history of coagulopathy such as hemophilia or Von Willebrand's disease or inherited thrombophilia.
- Hypertension not adequately controlled by medication (i.e. systolic blood pressure ≥ 150 and/or diastolic blood pressure ≥ 90 on at least two separate readings).
- History of congestive heart failure (CHF) greater than New York Heart Association (NYHA) Grade II.
- Participants who exhibit confusion, disorientation, or have a history of major psychiatric illness which may impair their understanding of the informed consent.
- Taking epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors within 3 months of study entry.
- Documented history of interstitial lung disease or pulmonary fibrosis.
- Known connective tissue disease.
- Patients who have participated in a clinical trial of an investigational drug within 12 months prior to enrollment.
- History of liver disease or AST and ALT ≥ 2.5 times ULN on screening.
- Consumption of green tea or supplements containing green tea or tea extract within 30 days prior to enrollment.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to polyphenon E, tea, or any of the inactive ingredients present in the active or placebo drug products, including gelatin capsules.
- Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
About this study
Official title: Phase I Study of Chemoprevention With Green Tea Polyphenon E (PPE) and the Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Erlotinib (OSI-774, Tarceva) in Patients With Premalignant Lesions of the Head and Neck
The purpose of this study is to test the preventive effects of a combination of drugs: polyphenon E (PPE) derived from green tea extracts, and erlotinib. Because this combination of drugs has not been tested in humans before for the prevention of cancer, it is not clear which dose of each agent will be optimal in combination.
We will test the safety of the combination of PPE and erlotinib and see what effects (good and/or bad) it has on the patient's premalignant lesion, and find the highest dose of each agent that can be given in combination without causing severe side effects.
- Conditions
- Cancer of Head and Neck, Neoplasms, Head and Neck
- Being tested
- Erlotinib, Green Tea Polyphenon E
- Keywords
- Pre-cancerous conditions, Head and neck tumors, Cancer of head and neck
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErlotinibDrug
Also called OSI-774, Tarceva
Participants will be given erlotinib orally (dose escalation from 50 mg, 75 mg, or 100 mg daily continuously for 6 cycles (each cycle is 28 days).
Green Tea Polyphenon EDietary supplement
Also called EGCG
Participants will also be given PPE orally (200 mg EGCG) three times daily for 6 cycles (each cycle is 28 days). PPE capsules will be taken on a full stomach, within one hour after eating a substantial meal.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib and Green Tea Polyphenon E | Experimental | Patients will receive erlotinib, at pre-defined dose level, with polyphenon E. Receives: Drug: Erlotinib; Dietary Supplement: Green Tea Polyphenon E |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of erlotinib when administered with a constant dose of green tea polyphenon E (PPE).
Define MTD as the dose level of erlotinib when administered with a constant dose of 200 mg (EGCG) TID of Green Tea Polyphenon E (PPE) to a patient results in a probability equal to θ = 0.33 that a dose-limiting toxicity (DLT) will be manifest within 1 cycle defined as 28 days.
Measured: Cytobrush/biopsy at three months
Secondary outcomes (1)
To assess the safety of the combination of PPE and erlotinib in patients receiving 3 different doses of erlotinib (50 mg, 75 mg, and 100 mg) in combination with PPE (200 mg EGCG TID) for 6 months.
Measured: Baseline, 3, 6, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2010 (estimated)
- Study startMar 2010
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of Head and NeckStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc, Polyphenon Pharma, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Dong Shin, Emory University
- Investigators
- Dong M. Shin, MD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01116336
- Sponsor's protocol ID
- IRB00014010
- Other IDs
- WCI1549-08, 5P50CA128613
- Status last verified
- Dec 2018
- First submitted
- 9 Apr 2010
- Last updated
- 5 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Chemoprevention With Green Tea Polyphenon E (PPE) and the Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Erlotinib (OSI-774, Tarceva) in Patients With Premalignant Lesions of the Head and Neck
- ClinicalTrials.gov ID
- NCT01116336
- Acronym / sponsor ID
- IRB00014010
- Conditions
- Cancer of Head and Neck, Neoplasms, Head and Neck
- Keywords
- Pre-cancerous conditions, Head and neck tumors, Cancer of head and neck
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc, Polyphenon Pharma, National Cancer Institute (NCI)
- Study start
- Mar 2010
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 5 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the preventive effects of a combination of drugs: polyphenon E (PPE) derived from green tea extracts, and erlotinib. Because this combination of drugs has not been tested in humans before for the prevention of cancer, it is not clear which dose of each agent will be optimal in combination.
We will test the safety of the combination of PPE and erlotinib and see what effects (good and/or bad) it has on the patient's premalignant lesion, and find the highest dose of each agent that can be given in combination without causing severe side effects.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib and Green Tea Polyphenon E | Experimental | Drug: Erlotinib, Dietary Supplement: Green Tea Polyphenon EPatients will receive erlotinib, at pre-defined dose level, with polyphenon E. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participants with premalignant lesions (mild dysplasia, moderate dysplasia, severe dysplasia, or carcinoma in situ) of the head and neck, as confirmed by biopsy within the 4 months prior to study entry or a treated primary T1N0 or T2N0 squamous cell carcinoma will be eligible.
- For patients with T1N0 or T2N0 treated squamous cell carcinoma, they must have been free of disease for a minimum period of 8 weeks, up to a maximum of 3 years following completion of surgery and/or radiotherapy.
- Eligible tumor and premalignant lesion sites include oral cavity (buccal mucosal, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, larynx (glottis, supraglottis, subglottis, epiglottis), hypopharynx paranasal sinus and nasal cavity.
- Patients with a treated tumor 1-node 0 (T1N0) or tumor 2-node 0 (T2N0) squamous cell carcinoma may have oral premalignant lesions (i.e., hyperplasia, dysplasia, carcinoma in situ) at the time of study entry (provided their Stage I or II disease has been definitively treated).
- Lesion sites include oral cavity (buccal mucosa, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, hypopharynx,larynx (glottis, supraglottis, subglottis, epiglottis), nasopharynx and paranasal sinuses.
Key exclusion criteria (19 listed)
- Because no dosing or adverse event data are currently available on the use of Polyphenon E in participants < 18 years of age, children are excluded from this study.
- Participants with hyperplasia, in absence of dysplasia or carcinoma in situ, will be excluded because there is possibly no benefit.
- Participants with acute intercurrent illness or those who had surgery within the preceding 4 weeks unless they have fully recovered.
- History of previous malignancies unless the cancer was stage I or II and rendered free of disease more than 1 year.
- Participants who are pregnant or breast feeding. Pregnant women are excluded from this study because Polyphenon E is an investigational agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Polyphenon E, breastfeeding should be discontinued if the mother is treated with Polyphenon E.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErlotinibAlso: OSI-774, TarcevaParticipants will be given erlotinib orally (dose escalation from 50 mg, 75 mg, or 100 mg daily continuously for 6 cycles (each cycle is 28 days). | Drug | Erlotinib and Green Tea Polyphenon E |
| Green Tea Polyphenon EAlso: EGCGParticipants will also be given PPE orally (200 mg EGCG) three times daily for 6 cycles (each cycle is 28 days). PPE capsules will be taken on a full stomach, within one hour after eating a substantial meal. | Dietary supplement | Erlotinib and Green Tea Polyphenon E |
Primary outcome
Maximum tolerated dose (MTD) of erlotinib when administered with a constant dose of green tea polyphenon E (PPE).
Time frame: Cytobrush/biopsy at three months
Define MTD as the dose level of erlotinib when administered with a constant dose of 200 mg (EGCG) TID of Green Tea Polyphenon E (PPE) to a patient results in a probability equal to θ = 0.33 that a dose-limiting toxicity (DLT) will be manifest within 1 cycle defined as 28 days.
1 secondary outcome
To assess the safety of the combination of PPE and erlotinib in patients receiving 3 different doses of erlotinib (50 mg, 75 mg, and 100 mg) in combination with PPE (200 mg EGCG TID) for 6 months.
Time frame: Baseline, 3, 6, and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dong M. Shin, MD principal investigator
Emory University Winship Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Erlotinib and Green Tea Polyphenon E in people with Cancer of Head and Neck and Neoplasms, Head and Neck, run by Emory University at 3 sites 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 23 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: finished, as of the sponsor's last update on 5 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (MTD) of erlotinib when administered with a constant dose of green tea polyphenon E (PPE). (time frame: Cytobrush/biopsy at three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Dec 2018.