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

Bladder Cancer Clinical Trial

— NRR  

Official title:

A Phase II Study of Erlotinib (Tarceva®) in Patients With Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00380029
• Other study ID #: LCCC 0521
• Secondary ID: P30CA016086UNC-L
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 22, 2006
• Last updated: November 22, 2016
• Start date: May 2006
• Est. completion date: August 2018

Study information

• Verified date: November 2016
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 pT3, 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 27
• Est. completion date: August 2018
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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:

• ECOG performance status 0-2

• Granulocyte count > 1,500/mm³

• Platelet count > 100,000/mm³

• Bilirubin normal

• AST and 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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• 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

Procedure:
• Radical Cystectomy
Will occur 4 weeks prior to dosing with erlotinib

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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: clinic — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological Complete Response Rate	Determine the pathological complete response rate (P0 rate)on histopathological, molecular, and genetic correlates before and after therapy to better understand the potential effects of EGFR inhibition in transitional cell carcinoma	4weeks	No
Secondary	Disease Recurrence and Progression rates after cystectomy	To determine disease recurrence/progression rates after cystectomy in patients treated with erlotinib	4 weeks after surgery	No
Secondary	Overall Survival Rate	Patients will be treated and followed until they demonstrate such evidence of disease recurrence (as demonstrated by cross-sectional imaging) or until 2 years after initiation of treatment. After 2 years, patients will be followed off of therapy for up to 5 years after trial entry for recurrence and survival	5 years	No
Secondary	Number of subjects experiencing adverse events	Toxicity will be graded per the CTCAE critera.	4 weeks	Yes