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.

Condition	Treatment or Intervention	Phase
transitional cell carcinoma of the bladder stage 0 bladder cancer stage I bladder cancer	Drug: erlotinib  Drug: green tea extract  Procedure: adjuvant therapy  Procedure: biologically based therapies  Procedure: cancer prevention intervention  Procedure: complementary and alternative therapy  Procedure: enzyme inhibitor therapy  Procedure: herbal medicine / botanical therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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 high-grade 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 9 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma (TCC) of the bladder
• Ta or T1 papillary TCC OR carcinoma in situ TCC
• Grade 2 or 3 disease
• Patients with grade 2 papillary tumors must meet at least 1 of the following criteria:
• At least 2 multiple, synchronous tumors
• A single tumor > 3 cm in size
• Newly diagnosed or recurrent tumor within the past 3 months AND rendered disease-free by prior standard surgery and/or intravesical therapy
• Transurethral resection of bladder within the past 3 months required
• No involvement of the upper urinary tract prior to or at the time of tumor resection
• Abdominal CT scan, intravenous pyelogram, or retrograde pyelogram must be performed within the past 12 months to rule out upper urinary tract tumor
• Former smoker AND ceased smoking for ≥ 12 months before study entry

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC > 3,000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 10 g/dL

Hepatic

• AST and ALT < 1.5 times upper limit of normal
• Bilirubin < 1.5 mg/dL

Renal

• Creatinine < 1.5 mg/dL

Pulmonary

• Obstructive lung disease (i.e., FEV_1 < 80% of predicted and FEV_1/FVC ratio < 90% of predicted) allowed provided chest radiograph does not demonstrate interstitial changes
• No idiopathic pulmonary fibrosis
• No evidence of parenchymal restrictive lung disease on pulmonary function test as indicated by the following criteria:
• Vital capacity and total lung capacity ≥ 80% of predicted
• DLCO ≥ 75% of predicted (corrected for hemoglobin)
• Patients with DLCO < 75% of predicted must undergo evaluation by a pulmonologist and/or high-resolution chest CT scan to rule out interstitial lung disease
• No asthma requiring active treatment
• No other interstitial lung disease

Ophthalmic

• No significant ophthalmic abnormalities
• No contact lens use

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No connective tissue disease, including the following:
• Scleroderma
• Rheumatoid arthritis
• Sjögren's syndrome
• Sarcoidosis
• No environmental or occupational metal or wood dust exposure
• No significant medical or psychiatric condition that would preclude study participation
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior intravesical BCG or interferon allowed
• Concurrent maintenance BCG allowed for patients who achieved a complete response to induction BCG therapy

Chemotherapy

• No prior chemotherapy except intravesical mitomycin or thiotepa

Endocrine therapy

• More than 4 weeks since prior high-dose steroids

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 4 weeks since prior anticancer therapy
• More than 4 weeks since prior experimental drugs
• More than 12 months since prior amiodarone, methotrexate, isoniazid, minocycline, or nitrofurantoin
• No normal consumption of > 5 cups of green tea daily
• No concurrent CYP3A4 inducers, including any of the following:
• Phenytoin
• Carbamazepine
• Hypericum perforatum (St. John's wort)
• Rifampin
• Grapefruit juice
• No concurrent CYP3A4/5 inhibitors or metabolizers (e.g., erythromycin or ketoconazole)
• No concurrent tricyclic antidepressants, including imipramine, dothiepin, and mianserin

Arizona
      Bladder Cancer Genitourinary Oncology, P.C., Phonix,  Arizona,  85032,  United States; Recruiting
California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1738,  United States; Recruiting
      Santa Monica UCLA Medical Center, Santa Monica,  California,  90404,  United States; Recruiting
      Veterans Affairs Medical Center - West Los Angeles, Los Angeles,  California,  90073,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting

Study chairs or principal investigators

Arie Belldegrun, MD, FACS,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000377681; UCLA-0301091-02; NCT00088946
Record last reviewed:  January 2005
Last Updated:  April 4, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088946
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08