Erlotinib Hydrochloride in Treating Patients With Bladder Cancer Undergoing Surgery

PRIMARY OBJECTIVES:

I. To determine if there is a difference in EGFR phosphorylation in normal appearing bladder
epithelium adjacent to tumor approximately 9-18 hours post-study dose, between patients
randomized to erlotinib hydrochloride (erlotinib) weekly as compared to placebo.

SECONDARY OBJECTIVES:

I. Assess the tolerance of high dose weekly erlotinib compared to placebo. II. Assess the
expression of phosphorylated EGF receptor in tumor tissue when available.

III. Assess the expression of e-cadherin and Ki67 in normal and abnormal urothelium.

IV. Assess the expression of phosphorylated ERK in normal and abnormal urothelium.

V. Assess limited pharmacokinetics of weekly erlotinib. VI. Assess the expression of p53 in
normal and abnormal urothelium. VII. Assess the expression of let-7 in normal and abnormal
urothelium. VIII. Exploratory assessment of urination symptoms in men.

OUTLINE: Patients are randomized to 1 of 2 treatment groups.

GROUP I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1, 8,
and 15. Patients then undergo transurethral resection of bladder tumor (TURBT) or cystectomy
on day 16.

GROUP II: Patients receive placebo PO QD on days 1, 8, and 15. Patients then undergo TURBT or
cystectomy on day 16.

After completion of study treatment, patients are followed up for 7-14 days.

Inclusion Criteria:

- Participants must have a confirmed or suspected invasive or non-invasive bladder tumor
(initial or recurrent) discovered on cystoscopy or radiologic imaging performed within
120 days of randomization

- Patients with muscle invasive bladder cancer (MIBC) must have never received and
currently be ineligible for cisplatin-based neoadjuvant chemotherapy due to any of the
following:

- Calculated creatinine clearance of < 60 ml/min

- Karnofsky performance status (KPS) < 80

- Solitary kidney or

- Patient refusal to undergo neoadjuvant chemotherapy

- The participant may have prior treatment for bladder tumor (excluding radiation
therapy) provided that treatment:

- Was completed greater than 30 days prior to the first dose of study agent

- Participants must be a candidate for a trans-urethral resection of the bladder tumor
(TURBT), cystectomy (partial or radical) or cystoscopy with biopsy at a participating
organization

- Karnofsky >= 60%

- White blood cells (WBC) >= 3000/mm^3

- Platelets >= 100,000mm^3

- Hemoglobin > 10 g/dL

- Alkaline phosphatase =< 1.5 x upper limit of normal

- Bilirubin =< 1.5 x upper limit of normal

- Aspartate aminotransferase (AST) =< 1.5 x upper limit of normal

- Alanine aminotransferase (ALT) =< 1.5 x upper limit of normal

- Bilirubin for Gilbert's =< 3.0 mg/dl

- A calculated creatinine clearance (Cockcroft Gault) of >= 30 ml/min

- Sodium >= 130 mg/dl and =< upper limit of normal

- Potassium >= 3.0 mg/dl and =< upper limit of normal

- 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

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Any treatment for the bladder tumor other than intravesical therapy between the
pre-study cystoscopy or radiologic imaging which identified the suspected bladder
tumor and the scheduled surgical removal or cystoscopy-guided biopsy of that tumor

- Any chemotherapy and/or radiation therapy received =< 3 months of study entry and any
immunotherapy received =< 6 months of study entry (with the execption of Bacillus
Calmette-Guerin [BCG] treatment)

- Any prior external beam radiation to the pelvis

- A concurrent skin rash or skin condition requiring treatment with a prescription
medication

- The following medications may not be taken within 24 hours of the first dose of study
agent or at any time while a participant is taking study agent

- Coumadin

- Strong CYP3A4 inhibitors including ketoconazole, atazanavir, boceprevir,
ceritinib, clarithromycin, cobicistat, darunavir, dasabuvir, idelalisib,
indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ombitasvir,
paritaprevir, posaconazole, ritonavir, saquinavir, telithromycin, troleandomycin,
voriconazole, and grapefruit or grapefruit juice

- CYP3A4 inducers including rifampicin, rifabutin, rifapentine, phenytoin,
carbamazepine, phenobarbital, primidone, enzalutamide, fosphenytoin, lumacaftor,
mitotane, and St. John's wort

- Agents which decrease gastric acid are allowed but should be avoided if possible

- Participants may resume inhibitors or inducers of CYP3A4 > 14 days after their
last dose of study agent

- Participants requiring daily use of non-steroidal anti-inflammatory drugs (NSAIDs),
with the exception of =< 81 mg aspirin per day; during study participation,
acetaminophen is preferred for treatment of pain; the use of NSAIDs, as needed for
pain, is discouraged

- Participants may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to erlotinib or clindamycin (topical agent for potential skin toxicity)

- An underlying predisposition to rectal or gastrointestinal bleeding or uncontrolled
intercurrent illness including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements

- Females who are pregnant or lactating may not participate in this study; females of
child-bearing potential must have a negative pregnancy test before starting study
agent; patients who have had a bilateral oophorectomy, hysterectomy, or are greater
than 1 year since their last menses are not considered to be of child-bearing
potential