Erlotinib Before and After Surgery in Treating Patients With Muscle-Invasive Bladder Cancer

NCT ID: NCT00380029

Last Updated: 2017-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2014-06-30

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well erlotinib works when given before and after surgery in treating patients with muscle-invasive bladder cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer.

Secondary

• Determine the pathological complete response rate in surgical specimens from patients treated with this drug.
• Determine recurrence and progression rates after cystectomy (up to 2 years after surgery) in patients treated with neoadjuvant and adjuvant erlotinib hydrochloride.
• Determine 2- and 5-year disease-free, disease-specific, and overall survival rates in patients treated with this drug.
• Determine the safety of this drug in these patients.

OUTLINE: This is an open-label study.

Patients receive oral erlotinib hydrochloride once daily for 4 weeks. Patients then undergo radical cystectomy with curative intent. Within 12 weeks after surgery, patients resume oral erlotinib hydrochloride* once daily for up to 2 years in the absence of disease progression or unacceptable toxicity.

Note: *Patients who are candidates for adjuvant chemotherapy (e.g., found to have pathologic stage T3 (pT3), Node positive (N+) disease) do not receive erlotinib hydrochloride after surgery.

Tumor tissue is obtained at baseline (at the original or confirmatory transurethral resection of the bladder tumor) and at the time of cystectomy for analysis of drug-specific and tissue-based biomarkers by western blot, immunohistochemistry, and gene array techniques. Histopathological, molecular, and genetic correlates are analyzed to better understand the potential effects of the epidermal growth factor receptor (EGFR) inhibition in transitional cell carcinoma and to determine the effect of neoadjuvant erlotinib on gene expression. Tumor tissue is also evaluated by real-time polymerase chain reaction to confirm drug effects on expected targets and on EGFR expression, activity, and affected signaling pathways in the disease state and by microarray analysis to define expression phenotypes correlating with outcome, distinguish responders from nonresponders, and determine effects of drug treatment on gene expression in disease.

Patients are followed periodically for up to 5 years after surgery.

Conditions

Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Erlotinib

erlotinib given before and after transurethral resection of a bladder tumor, TURBT

Group Type: EXPERIMENTAL

Erlotinib

Intervention Type: DRUG

Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy. In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression

Radical Cystectomy

Intervention Type: PROCEDURE

Will occur 4 weeks prior to dosing with erlotinib

Interventions

Erlotinib

Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy. In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression

Intervention Type: DRUG

Radical Cystectomy

Will occur 4 weeks prior to dosing with erlotinib

Intervention Type: PROCEDURE

Other Intervention Names

Tarceva

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed muscle-invasive bladder cancer, meeting the following criteria:

• Clinical stage T2 disease
• No locally-extensive clinical stage T3 or T4 disease
• No metastatic disease (N+, M+) by physical exam or radiologic evaluation
• Must have undergone prior initial or confirmatory transurethral resection of the bladder tumor (TURBT)
• Candidate for and has agreed to undergo radical cystectomy with curative intent
• No non-transitional cell carcinoma histologies

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Granulocyte count > 1,500/mm³
• Platelet count > 100,000/mm³
• Bilirubin normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times upper limit of normal
• Creatinine normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No contraindication to erlotinib hydrochloride or other tyrosine kinase inhibitors

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy or systemic chemotherapy for bladder cancer

• Prior single-dose mitomycin C allowed at the time of TURBT
• Prior 6- or 12-week course of adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with or without recombinant interferon alfa-2a allowed
• At least 4 weeks since other prior or concurrent radiotherapy, chemotherapy, or hormonal therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OSI Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raj S. Pruthi, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

References

Pruthi RS, Nielsen M, Heathcote S, Wallen EM, Rathmell WK, Godley P, Whang Y, Fielding J, Schultz H, Grigson G, Smith A, Kim W. A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy: clinical and pathological results. BJU Int. 2010 Aug;106(3):349-54. doi: 10.1111/j.1464-410X.2009.09101.x. Epub 2010 Jan 19.

Reference Type: RESULT

PMID: 20089114 (View on PubMed)

Related Links

http://unclineberger.org

UNC Lineberger Comprehensive Cancer Center

Other Identifiers

P30CA016086

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC 0521

Identifier Type: -

Identifier Source: org_study_id