Erlotinib Hydrochloride in Treating Patients With Bladder Cancer Undergoing Surgery
Recurrent Bladder Carcinoma - Stage I Bladder Cancer - Stage II Bladder Cancer - Stage III Bladder Cancer
Conditions: official terms
Urinary Bladder Neoplasms
Study Type
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Name: Erlotinib Hydrochloride Type: Drug
Name: Laboratory Biomarker Analysis Type: Other
Name: Pharmacological Study Type: Other
Name: Placebo Type: Other
Name: Therapeutic Conventional Surgery Type: Procedure
Overall Status
This randomized phase II trial studies how well erlotinib hydrochloride works in treating patients with bladder cancer undergoing surgery. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description

I. To determine if there is a difference in epidermal growth factor receptor (EGFR) phosphorylation in bladder epithelium (adjacent normal appearing) 24 hours post-study dose, between patients randomized to erlotinib (erlotinib hydrochloride) weekly as compared to placebo.


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

III. Assess the expression of cadherin 1, type 1 (e-cadherin) and marker of proliferation Ki-67 (Ki67) in normal and abnormal urothelium.

IV. Assess the expression of phosphorylated extracellular regulated kinase (ERK) in normal and abnormal urothelium.

V. Assess limited pharmacokinetics of weekly erlotinib. VI. Assess the expression of tumor protein 53 (p53) in normal and abnormal urothelium.

VII. Assess the expression of lethal-7 (let-7) in normal and abnormal urothelium.

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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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 60 days of randomization

- Patients with muscle invasive bladder cancer (MIBC) must 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 screening/baseline visit

- Occurred prior to the cystoscopy or radiologic imaging used to determine participant eligibility

- 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

- International normalized ratio (INR) =< 1.2

- Alkaline phosphatase =< upper limit of normal

- Bilirubin =< upper limit of normal

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

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

- 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

- Chloride =< upper limit of normal

- Bicarbonate =< upper limit of normal

- Calcium =< 11.2 mg/dl

- 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 bladder cancer including surgery (other than a biopsy) intravesical therapy, adjuvant or neoadjuvant chemotherapy within 30 days prior to the pre-study cystoscopy or radiologic imaging which identified the suspected bladder tumor

- Any treatment for the bladder tumor (including intravesical therapy, adjuvant or neoadjuvant chemotherapy) 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 evidence of other cancers (excluding non-melanoma skin cancer) or metastatic disease

- Any prior pelvic radiation

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

- Concurrent systemic chemotherapy for any other cancer, excluding non-melanoma skin cancer

- 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

- Potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors including ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice

- CYP3A4 inducers including rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's Wort

- Proton pump inhibitors (e.g. omeprazole); other agents which decrease gastric acid are allowed but should be avoided if possible

- Participants may resume use of proton pump inhibitors or agents which increase gastric pH > 24 hours following their last dose of study agent unless otherwise instructed by their treating physician

- 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
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Status: Recruiting
Contact: Trinity J. Bivalacqua - 443-287-0385 -
Lahey Hospital and Medical Center
Burlington, Massachusetts, United States
Status: Recruiting
Contact: Jason R. Gee - 781-744-8334 -
University of Rochester
Rochester, New York, United States
Status: Recruiting
Contact: Edward M. Messing - 585-275-3345 -
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States
Status: Recruiting
Contact: Neal D. Shore - 843-839-1679 -
Urology San Antonio Research PA
San Antonio, Texas, United States
Status: Recruiting
Contact: Daniel R. Saltzstein - 210-617-4116 -
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Status: Recruiting
Contact: Tracy M. Downs - 608-263-9534 -
Start Date
October 2014
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Record processing date processed this data on July 28, 2015 page