Cisplatin, Bevacizumab, and Gemcitabine Followed by Surgery, Bevacizumab, and Paclitaxel in Treating Patients With Locally Advanced Nonmetastatic Bladder Cancer That Can Be Removed By Surgery
RATIONALE: Drugs used in chemotherapy, such as cisplatin, gemcitabine, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving cisplatin, bevacizumab, and gemcitabine followed by surgery, bevacizumab, and paclitaxel works in treating patients with locally advanced nonmetastatic bladder cancer that can be removed by surgery.
Drug: gemcitabine hydrochloride
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Neo-Adjuvant Cisplatin, Gemcitabine & Bevacizumab, Followed by Radical Cystectomy for Patients With Muscle Invasive, Resectable, Non-Metastatic Transitional Cell Carcinoma (TCC) of the Bladder|
- Overall pT0 response rate [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
- Determine the pT0 status (pathologic complete remission rate, no evidence of disease on cystectomy specimen) in patients with muscle-invasive, resectable, nonmetastatic transitional cell carcinoma (TCC) of the bladder treated with neoadjuvant cisplatin, bevacizumab, and gemcitabine hydrochloride followed by radical cystectomy and adjuvant bevacizumab and paclitaxel.
- Determine if urinary survivin and urocytogenetics can predict responses in patients with muscle invasive, resectable, non-metastatic TCC of the bladder treated with neoadjuvant cisplatin and gemcitabine chemotherapy with bevacizumab.
- Evaluate the progression-free and median survival in patients treated with neo-adjuvant cisplatin and gemcitabine hydrochloride chemotherapy with bevacizumab followed by radical cystectomy.
- Determine the feasibility, tolerability and toxicity of neoadjuvant cisplatin and gemcitabine hydrochloride with bevacizumab in patients with muscle invasive, resectable, nonmetastatic transitional cell carcinoma (TCC) of the bladder.
- Correlate pT0 on cystoscopy with pT0 on radical cystectomy in patients treated with neoadjuvant cisplatin and gemcitabine hydrochloride chemotherapy with bevacizumab in patients with muscle invasive, resectable, nonmetastatic transitional cell carcinoma (TCC) of the bladder.
- Determine the influence of adjuvant paclitaxel plus bevacizumab (in pathologic non-complete responders) on progression-free and overall survival rates.
- Determine the safety of bevacizumab use in the adjuvant setting in therapy of locally advanced bladder cancer.
- Determine the rate of postoperative complications, following treatment with neoadjuvant therapy (cisplatin, gemcitabine hydrochloride, and bevacizumab) and radical cystectomy.
OUTLINE: This is a multicenter study.
- Neoadjuvant therapy: Patients receive cisplatin IV over 60 minutes and bevacizumab IV over 30-90 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with nonmetastatic disease at 12 weeks proceed to surgery at least 30 days later.
- Surgery: Patients undergo radical cystectomy. Patients who achieve pT0 status (pathologic complete remission rate, no evidence of disease on cystectomy specimen) are observed off study. Patients with evidence of disease proceed to adjuvant therapy.
- Adjuvant therapy: Patients receive bevacizumab IV over 30-90 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 6 years.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268450
|United States, South Carolina|
|Hollings Cancer Center at Medical University of South Carolina|
|Charleston, South Carolina, United States, 29425|
|McLeod Regional Medical Center|
|Florence, South Carolina, United States, 29501|
|Lowcountry Hematology and Oncology, PA|
|Mount Pleasant, South Carolina, United States, 29464-3233|
|Gibbs Regional Cancer Center at Spartanburg Regional Medical Center|
|Spartanburg, South Carolina, United States, 29303|
|Study Chair:||Andrew S. Kraft, MD||Medical University of South Carolina|