Clinical trial NCT00268450: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: transitional cell carcinoma of the bladder
stage III bladder cancer
stage II bladder cancer
recurrent bladder cancer
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2005-12-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Complete Remission Rate
timeFrame: From day of first treatment until after cycle 3
Secondary outcomes:
measure: Urinary Survivin Levels
timeFrame: Baseline, week 6 and week 12
measure: Urinary Cytogenitics
timeFrame: baseline and week 12
measure: Progression Free Survival
timeFrame: from first treatment until time of progression or death, whichever comes first
measure: Median Overall Surivial
timeFrame: from first treatment until death
measure: Percentage of Planned Dose Received
timeFrame: from first treatment until end of week 12
measure: Rate of Post-operative Complications
timeFrame: from first treatment until up to 48 hours after surgery.
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Mount Pleasant
country: United States
facility: Lowcountry Hematology and Oncology, PA
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Andrew S. Kraft, MD
role: STUDY_CHAIR
affiliation: Medical University of South Carolina, Hollings Cancer Center
name: Gustavo Leone
role: STUDY_CHAIR
References: