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Erlotinib and Green Tea Extract (Polyphenon® E) in Preventing Cancer Recurrence in Former Smokers Who Have Undergone Surgery for Bladder Cancer

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Polyphenon E
erlotinib hydrochloride
Erlotinib placebo
Polyphenon E
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring transitional cell carcinoma of the bladder, stage 0 bladder cancer, stage I bladder cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants must be former smokers and have ceased smoking at study entry. Participants with any previous history of prior cancer diagnosis of Grade 1, 2, or 3, Ta or T1 papillary TCC, or CIS TCC, histologically confirmed, with a newly diagnosed or recurrent tumor within 6 months of accrual who are rendered disease free by standard of care. Patients with Grade 1 papillary tumors must meet at least one of the following additional criteria: multiple, synchronous tumors (>2) a single tumor greater than 1 cm in size At study entry, patients must have no evidence of disease Participants may have been previously treated with intravesical therapy. Age>18 years Transurethral resection of bladder tumor within 6 months prior to entry on to study Participants must have a signed written informed consent Agreement with complete abstinence from heterosexual intercourse or with the use of contraception during the treatment phase in women of childbearing potential Negative pregnancy test in women of childbearing potential Patients must have adequate bone marrow function at study entry (WBC>3000, platelets>100000/mm3, and hemoglobin>10g/dl) Patients must have satisfactory renal and hepatic function, defined as plasma creatinine of < 1.5mg/dl, total bilirubin < 1.5, and AST/ALT < 1.5 x the upper limit of normal Patients with evidence of obstructive lung disease as the etiology of a low diffusing capacity will still be eligible as long as the chest radiograph does not demonstrate interstitial changes Exclusion Criteria: Prior chemotherapy or radiotherapy Prior (within 2 years) or concurrent malignancies, except non-melanomatous skin tumors or carcinoma in situ of the cervix Significant medical or psychiatric condition that would make the participant a poor protocol candidate TCC greater than or equal to T2 at most recent diagnosis Involvement of the upper urinary tract prior to or at the time of initial tumor resection Prior treatment with experimental drugs, high dose steroids, or with any other cancer treatment within 4 weeks prior to the first dose of study drug and for the duration of the study Positive pregnancy test at any time throughout the course of the study Normal consumption of greater than 5 cups of green tea daily Participants taking a known CYP 3A4 inducer or food products and medications known to be inhibitors or metabolized by CYP3A4/5 such as erythromycin, ketoconazole, etc. will be excluded since these drugs may be expected to result in altered exposure of Erlotinib ECOG performance status > 1 History of idiopathic pulmonary fibrosis or other interstitial lung disease Use of tricyclic antidepressants, including imipramine, dothiepin, and mianserin Use within the last 12 months of amiodarone, methotrexate, isoniazid, minocycline, or nitrofurantoin History of environmental or occupational metal dust or wood dust exposure History of connective tissue disease, including scleroderma, rheumatoid arthritis, Sjogren's Syndrome, or sarcoid Significant ophthalmologic abnormalities or patients using contact lenses Evidence of interstitial lung disease on chest radiograph Patients without obvious interstitial lung disease on chest radiograph will be excluded if they have evidence of parenchymal restrictive lung disease on pulmonary function testing as identified by the following criteria: Both vital capacity and total lung capacity <80% of predicted value A diffusing capacity of the lung for carbon monoxide, corrected for hemoglobin, < 75% of predicted value

Sites / Locations

  • Bladder Cancer Genitourinary Oncology, PC
  • Veterans Affairs Medical Center - West Los Angeles
  • Jonsson Comprehensive Cancer Center at UCLA
  • Santa Monica UCLA Medical Center
  • Mayo Clinic Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Arm 1

Arm 2

Arm 3

Arm Description

Polyphenon E plus erlotinib placebo daily for 12 months.

Erlotinib and Polyphenon E placebo daily for 12 months.

Erlotinib placebo and Polyphenon E placebo daily for 12 months.

Outcomes

Primary Outcome Measures

Evaluate the effects of a daily oral dose of polyphenon E, erlotinib, or placebo on subjects who are former smokers with a history of superficial bladder cancer on the bladder cancer recurrence rate at two years of any stage or grade of bladder cancer.

Secondary Outcome Measures

To address the unmet need in medical management of superficial bladder cancer as an adjunct to standard of care.
Assess toxicities associated with daily oral dosing of polyphenon E or erlotinib in subjects at risk for bladder tumor recurrence and to define a safe and effective prevention dose of erlotinib.
Correlate the modulation of one or more biomarkers with recurrence of bladder cancer confirming the value as a surrogate endpoint biomarker for bladder cancer recurrence and/or progression.
To assess the risk of clinical bladder cancer progression in patients treated with polyphenon E, erlotinib or placebo.

Full Information

First Posted
August 4, 2004
Last Updated
July 30, 2020
Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00088946
Brief Title
Erlotinib and Green Tea Extract (Polyphenon® E) in Preventing Cancer Recurrence in Former Smokers Who Have Undergone Surgery for Bladder Cancer
Official Title
Parallel, Randomized, Double-Blind, Placebo Controlled Phase II Adjuvant Studies of Erlotinib and Polyphenon E to Prevent the Recurrence and Progression of Tobacco-Related, Superficial Bladder Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
July 2006 (Actual)
Study Completion Date
July 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Green tea extract (Polyphenon® E) contains certain ingredients that may slow the growth of tumor cells and prevent the recurrence of cancer. Giving erlotinib or green tea extract after surgery may kill any remaining tumor cells and may prevent the recurrence of bladder cancer. PURPOSE: This randomized phase II trial is studying how well giving erlotinib together with green tea extract works in preventing cancer recurrence in former smokers who have undergone surgery for bladder cancer.
Detailed Description
OBJECTIVES: Primary Compare the effects of erlotinib vs green tea extract (Polyphenon® E) vs placebo on the 2-year recurrence rate in former smokers with resected superficial transitional cell carcinoma of the bladder. Develop an effective chemopreventative strategy (as an adjunct to standard care) for the medical management of superficial bladder cancer in these patients. Secondary Determine the toxic effects associated with these drugs in these patients. Determine a safe and effective chemopreventative dose of erlotinib in these patients. Correlate the modulation of 1 or more biomarkers with bladder cancer recurrence and/or progression in patients treated with these drugs. Determine the risk of clinical bladder cancer progression in patients treated with these drugs. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (Ta vs T1 vs carcinoma in situ) and participating center. Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive oral erlotinib and oral green tea extract (Polyphenon® E) placebo once daily. Arm II: Patients receive oral green tea extract (Polyphenon® E) and oral erlotinib placebo once daily. Arm III: Patients receive oral erlotinib placebo and oral green tea extract placebo once daily. In all arms, treatment continues for 12 months in the absence of disease recurrence or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 330 patients (110 per treatment arm) will be accrued for this study within 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
transitional cell carcinoma of the bladder, stage 0 bladder cancer, stage I bladder cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Polyphenon E plus erlotinib placebo daily for 12 months.
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Erlotinib and Polyphenon E placebo daily for 12 months.
Arm Title
Arm 3
Arm Type
Placebo Comparator
Arm Description
Erlotinib placebo and Polyphenon E placebo daily for 12 months.
Intervention Type
Dietary Supplement
Intervention Name(s)
Polyphenon E
Other Intervention Name(s)
green tea extract
Intervention Description
4-200mg capsules PO daily for 12 months
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
Tarceva
Intervention Description
100 mg PO daily for 12 months
Intervention Type
Other
Intervention Name(s)
Erlotinib placebo
Intervention Description
identical to Erlotinib in look and appearance of dosing.
Intervention Type
Other
Intervention Name(s)
Polyphenon E
Intervention Description
identical to Polyphenon E in look and appearance of dosing.
Primary Outcome Measure Information:
Title
Evaluate the effects of a daily oral dose of polyphenon E, erlotinib, or placebo on subjects who are former smokers with a history of superficial bladder cancer on the bladder cancer recurrence rate at two years of any stage or grade of bladder cancer.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To address the unmet need in medical management of superficial bladder cancer as an adjunct to standard of care.
Time Frame
2 years
Title
Assess toxicities associated with daily oral dosing of polyphenon E or erlotinib in subjects at risk for bladder tumor recurrence and to define a safe and effective prevention dose of erlotinib.
Time Frame
2 years
Title
Correlate the modulation of one or more biomarkers with recurrence of bladder cancer confirming the value as a surrogate endpoint biomarker for bladder cancer recurrence and/or progression.
Time Frame
2 years
Title
To assess the risk of clinical bladder cancer progression in patients treated with polyphenon E, erlotinib or placebo.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must be former smokers and have ceased smoking at study entry. Participants with any previous history of prior cancer diagnosis of Grade 1, 2, or 3, Ta or T1 papillary TCC, or CIS TCC, histologically confirmed, with a newly diagnosed or recurrent tumor within 6 months of accrual who are rendered disease free by standard of care. Patients with Grade 1 papillary tumors must meet at least one of the following additional criteria: multiple, synchronous tumors (>2) a single tumor greater than 1 cm in size At study entry, patients must have no evidence of disease Participants may have been previously treated with intravesical therapy. Age>18 years Transurethral resection of bladder tumor within 6 months prior to entry on to study Participants must have a signed written informed consent Agreement with complete abstinence from heterosexual intercourse or with the use of contraception during the treatment phase in women of childbearing potential Negative pregnancy test in women of childbearing potential Patients must have adequate bone marrow function at study entry (WBC>3000, platelets>100000/mm3, and hemoglobin>10g/dl) Patients must have satisfactory renal and hepatic function, defined as plasma creatinine of < 1.5mg/dl, total bilirubin < 1.5, and AST/ALT < 1.5 x the upper limit of normal Patients with evidence of obstructive lung disease as the etiology of a low diffusing capacity will still be eligible as long as the chest radiograph does not demonstrate interstitial changes Exclusion Criteria: Prior chemotherapy or radiotherapy Prior (within 2 years) or concurrent malignancies, except non-melanomatous skin tumors or carcinoma in situ of the cervix Significant medical or psychiatric condition that would make the participant a poor protocol candidate TCC greater than or equal to T2 at most recent diagnosis Involvement of the upper urinary tract prior to or at the time of initial tumor resection Prior treatment with experimental drugs, high dose steroids, or with any other cancer treatment within 4 weeks prior to the first dose of study drug and for the duration of the study Positive pregnancy test at any time throughout the course of the study Normal consumption of greater than 5 cups of green tea daily Participants taking a known CYP 3A4 inducer or food products and medications known to be inhibitors or metabolized by CYP3A4/5 such as erythromycin, ketoconazole, etc. will be excluded since these drugs may be expected to result in altered exposure of Erlotinib ECOG performance status > 1 History of idiopathic pulmonary fibrosis or other interstitial lung disease Use of tricyclic antidepressants, including imipramine, dothiepin, and mianserin Use within the last 12 months of amiodarone, methotrexate, isoniazid, minocycline, or nitrofurantoin History of environmental or occupational metal dust or wood dust exposure History of connective tissue disease, including scleroderma, rheumatoid arthritis, Sjogren's Syndrome, or sarcoid Significant ophthalmologic abnormalities or patients using contact lenses Evidence of interstitial lung disease on chest radiograph Patients without obvious interstitial lung disease on chest radiograph will be excluded if they have evidence of parenchymal restrictive lung disease on pulmonary function testing as identified by the following criteria: Both vital capacity and total lung capacity <80% of predicted value A diffusing capacity of the lung for carbon monoxide, corrected for hemoglobin, < 75% of predicted value
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arie Belldegrun, MD, FACS
Organizational Affiliation
Jonsson Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bladder Cancer Genitourinary Oncology, PC
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Facility Name
Veterans Affairs Medical Center - West Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
Santa Monica UCLA Medical Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Erlotinib and Green Tea Extract (Polyphenon® E) in Preventing Cancer Recurrence in Former Smokers Who Have Undergone Surgery for Bladder Cancer

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