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
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
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.
OBJECTIVES:
Primary
Secondary
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.
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.
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:
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: