Clinical trial NCT00380029: Erlotinib Before and After Surgery in Treating Patients With Muscle-Invasive Bladder Cancer
Official title: A Phase II Study of Erlotinib (Tarceva®) in Patients With Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: stage II bladder cancer
transitional cell carcinoma of the bladder
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: OSI Pharmaceuticals
name: National Cancer Institute (NCI)
First posted: 2006-09-25
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: EGFR Activation Signal (AKT2) Expression to Predict Sensitivity to Erlotinib
timeFrame: 4 weeks before treatment and 4 weeks post treatment
Secondary outcomes:
measure: Pathological Complete Response Rate
timeFrame: 4 weeks
measure: Disease Recurrence and Progression Rates After Cystectomy
timeFrame: 2 years
measure: Overall Survival Rate
timeFrame: 25 months
measure: Number of Subjects Experiencing Adverse Events
timeFrame: 4 weeks - 2 years following surgery
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Raj S. Pruthi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.