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 - Full Text View

Sponsored by:	Medical University of South Carolina
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00268450

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	Drug: bevacizumab Drug: cisplatin Drug: gemcitabine hydrochloride Drug: paclitaxel Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase II

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Cisplatin Gemcitabine hydrochloride Gemcitabine Paclitaxel Bevacizumab Phenylephrine Guaifenesin Naphazoline Naphazoline hydrochloride Oxymetazoline Oxymetazoline hydrochloride Phenylephrine hydrochloride Phenylpropanolamine Phenylpropanolamine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall pT0 response rate [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	September 2005
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Detailed Description:

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
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Clinical Trials Office - Gibbs Regional Cancer Center 800-486-5941
Hollings Cancer Center at Medical University of South Carolina	Recruiting
Charleston, South Carolina, United States, 29425
Contact: Clinical Trials Office - Hollings Cancer Center at Medical Uni 843-792-9321
Lowcountry Hematology and Oncology, PA	Recruiting
Mount Pleasant, South Carolina, United States, 29464-3233
Contact: Uzair B. Chaudhary, MD 843-286-5741
McLeod Regional Medical Center	Recruiting
Florence, South Carolina, United States, 29501
Contact: Clinical Trials Office - McLeod Regional Medical Center 843-679-7256

Sponsors and Collaborators

Medical University of South Carolina

Investigators

Study Chair:

Andrew S. Kraft, MD

Medical University of South Carolina

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Hollings Cancer Center at Medical University of South Carolina ( Andrew S. Kraft )
Study ID Numbers:	CDR0000454937, MUSC-AVF-3312, MUSC-HR-15537, GENENTECH-AVF-3312, MUSC-CTO-100892
Study First Received:	December 20, 2005
Last Updated:	December 2, 2008
ClinicalTrials.gov Identifier:	NCT00268450
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

transitional cell carcinoma of the bladder
stage III bladder cancer
stage II bladder cancer
recurrent bladder cancer

Study placed in the following topic categories:

Cystocele
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Urogenital Neoplasms
Bevacizumab
Carcinoma, Transitional Cell
Urologic Neoplasms
Transitional cell carcinoma
Recurrence
Carcinoma
Naphazoline

Oxymetazoline
Cisplatin
Urologic Diseases
Guaifenesin
Phenylephrine
Paclitaxel
Phenylpropanolamine
Gemcitabine
Urinary tract neoplasm
Neoplasms, Glandular and Epithelial
Bladder neoplasm

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Mitosis Modulators
Physiological Effects of Drugs
Enzyme Inhibitors
Antimitotic Agents

Angiogenesis Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators
Growth Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 15, 2009