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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00268450
• Other study ID #: CDR0000454937
• Secondary ID: MUSC-AVF-3312MUS
• Status: Terminated
• Phase: Phase 2
• Start date: September 21, 2005
• Est. completion date: April 2012

Study information

• Verified date: May 2018
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms

Intervention

Biological:
• bevacizumab
Before surgery: given as a 15mg/kg IV over 90 minutes every 21 days for 4 cycles After surgery: given as a 15mg/kg IV over 90 minutes every 21 days for 3 cycles

Drug:
• cisplatin
Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles
• gemcitabine hydrochloride
Before surgery: given as a 1000mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle for 4 cycles
• paclitaxel
After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles

Procedure:
• cysectomy

Locations

Country	Name	City	State
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Lowcountry Hematology and Oncology, PA	Mount Pleasant	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of South Carolina

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission Rate		From day of first treatment until after cycle 3
Secondary	Urinary Survivin Levels		Baseline, week 6 and week 12
Secondary	Urinary Cytogenitics		baseline and week 12
Secondary	Progression Free Survival		from first treatment until time of progression or death, whichever comes first
Secondary	Median Overall Surivial		from first treatment until death
Secondary	Percentage of Planned Dose Received		from first treatment until end of week 12
Secondary	Rate of Post-operative Complications		from first treatment until up to 48 hours after surgery.