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
This study has been completed.
Sponsor:
Medical University of South Carolina
Information provided by:
Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00268450
First received: December 20, 2005
Last updated: April 26, 2012
Last verified: April 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Bladder Cancer |
Biological: bevacizumab Drug: cisplatin Drug: gemcitabine hydrochloride Drug: paclitaxel Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy |
Phase 2 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
bladder cancer
Drug Information available for:
Cisplatin
Paclitaxel
Gemcitabine
Gemcitabine hydrochloride
Bevacizumab
U.S. FDA Resources
Further study details as provided by Medical University of South Carolina:
Primary Outcome Measures:
- Overall pT0 response rate [ Designated as safety issue: No ]
| Estimated Enrollment: | 25 |
| Study Start Date: | September 2005 |
| Study Completion Date: | April 2012 |
| Primary Completion Date: | April 2012 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed transitional cell cancer (TCC) of the bladder
Staged as follows:
- Muscle invasive (T2-T4a)
Node negative (N0)
- No histologically or cytologically proven lymph node metastases
Nonmetastatic (M0)
- No evidence of distant metastases
- Resectable disease
- Able to begin protocol treatment within 6 weeks after transurethral resection and cystoscopic evaluation
- No central nervous system or brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status of 0-2
- Karnofsky 60-100%
- White blood cell count ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST(SGOT) and ALT(SGPT) ≤ 2 times upper limit of normal
- Bilirubin ≤1.5 mg/dL
- Creatinine clearance ≥ 60 mL/min
- Urine protein/creatinine ratio < 1.0
- Blood pressure ≤150/100 mm Hg
- No prohibitive medical risks for chemotherapy
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, gemcitabine hydrochloride, or paclitaxel
- No unstable angina
- No history of myocardial infarction within the past 6 months
- No cardiac arrhythmias
- No New York Heart Association (NYHA) congestive heart failure ≥ grade 2
- No history of stroke within the past 6 months
- No clinically significant peripheral vascular disease
- No evidence of bleeding diathesis or coagulopathy
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No serious nonhealing wound, ulcer, or bone fracture
- No psychiatric illness or other psychosocial situation that would limit ability to comply with study and/or follow-up procedures
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must agree to use adequate contraception prior to study entry and for the duration of study participation
- No significant traumatic injury with in the past 28 days
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy
- No prior pelvic radiation therapy
- More than 4 weeks since prior participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- No concurrent participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- No major surgical procedure or open biopsy within the past 28 days
- No anticipation of need for major surgical procedure during the course of the study
- No minor surgical procedures, fine-needle aspirations, or core biopsies within the past 7 days
No concurrent treatment with hormones or other chemotherapeutic agents except the following:
- Steroids given for adrenal failure
- Hormones administered for nondisease-related conditions (e.g., insulin for diabetes)
- Intermittent use of dexamethasone as an antiemetic in solid tumor protocols
- No other concurrent investigational or commercial agents or therapies
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268450
Locations
| 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 | |
Sponsors and Collaborators
Medical University of South Carolina
Investigators
| Study Chair: | Andrew S. Kraft, MD | Medical University of South Carolina |
More Information
Additional Information:
No publications provided
| Responsible Party: | Andrew S. Kraft, Hollings Cancer Center at Medical University of South Carolina |
| ClinicalTrials.gov Identifier: | NCT00268450 History of Changes |
| Other Study ID Numbers: | CDR0000454937, MUSC-AVF-3312, MUSC-HR-15537, GENENTECH-AVF-3312, MUSC-CTO-100892 |
| Study First Received: | December 20, 2005 |
| Last Updated: | April 26, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Medical University of South Carolina:
|
transitional cell carcinoma of the bladder stage III bladder cancer stage II bladder cancer recurrent bladder cancer |
Additional relevant MeSH terms:
|
Urinary Bladder Neoplasms Carcinoma, Transitional Cell Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Urinary Bladder Diseases Urologic Diseases Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Adjuvants, Immunologic Gemcitabine Bevacizumab Cisplatin |
Paclitaxel Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Radiation-Sensitizing Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Tubulin Modulators |
ClinicalTrials.gov processed this record on May 22, 2013