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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

Primary Purpose

Bladder Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
cisplatin
gemcitabine hydrochloride
paclitaxel
cysectomy
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring transitional cell carcinoma of the bladder, stage III bladder cancer, stage II bladder cancer, recurrent bladder cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hollings Cancer Center at Medical University of South Carolina
  • McLeod Regional Medical Center
  • Lowcountry Hematology and Oncology, PA
  • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

study intervention

Arm Description

Neo-adjuvant cisplatin, gemcitabine and bevacizumab followed by radical cystectomy. Patients without residual disease will enter follow up after surgery. Patients with residual disease will receive adjuvant therapy with bevacizumab and ciaplatin.

Outcomes

Primary Outcome Measures

Complete Remission Rate

Secondary Outcome Measures

Urinary Survivin Levels
Urinary Cytogenitics
Progression Free Survival
Median Overall Surivial
Percentage of Planned Dose Received
Rate of Post-operative Complications

Full Information

First Posted
December 20, 2005
Last Updated
June 13, 2018
Sponsor
Medical University of South Carolina
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1. Study Identification

Unique Protocol Identification Number
NCT00268450
Brief Title
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

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Terminated
Study Start Date
September 21, 2005 (Actual)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
transitional cell carcinoma of the bladder, stage III bladder cancer, stage II bladder cancer, recurrent bladder cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
study intervention
Arm Type
Experimental
Arm Description
Neo-adjuvant cisplatin, gemcitabine and bevacizumab followed by radical cystectomy. Patients without residual disease will enter follow up after surgery. Patients with residual disease will receive adjuvant therapy with bevacizumab and ciaplatin.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
avastin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Description
Before surgery: given as a 1000mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle for 4 cycles
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles
Intervention Type
Procedure
Intervention Name(s)
cysectomy
Primary Outcome Measure Information:
Title
Complete Remission Rate
Time Frame
From day of first treatment until after cycle 3
Secondary Outcome Measure Information:
Title
Urinary Survivin Levels
Time Frame
Baseline, week 6 and week 12
Title
Urinary Cytogenitics
Time Frame
baseline and week 12
Title
Progression Free Survival
Time Frame
from first treatment until time of progression or death, whichever comes first
Title
Median Overall Surivial
Time Frame
from first treatment until death
Title
Percentage of Planned Dose Received
Time Frame
from first treatment until end of week 12
Title
Rate of Post-operative Complications
Time Frame
from first treatment until up to 48 hours after surgery.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew S. Kraft, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gustavo Leone
Organizational Affiliation
Medical University of South Carolina, Hollings Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Hollings Cancer Center at Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
McLeod Regional Medical Center
City
Florence
State/Province
South Carolina
ZIP/Postal Code
29501
Country
United States
Facility Name
Lowcountry Hematology and Oncology, PA
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464-3233
Country
United States
Facility Name
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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