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

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

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.

Study Overview

• Status: Terminated
• Conditions: Bladder Cancer
• Intervention / Treatment: Biological: bevacizumab; Drug: cisplatin; Drug: gemcitabine hydrochloride; Drug: paclitaxel; Procedure: cysectomy

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Florence, South Carolina, United States, 29501
      • McLeod Regional Medical Center
    • Mount Pleasant, South Carolina, United States, 29464-3233
      • Lowcountry Hematology and Oncology, PA
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: study intervention; 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.

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; Other Names: avastin; Drug: cisplatin; Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles; Drug: 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; Drug: paclitaxel; After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles; Procedure: cysectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete Remission Rate	From day of first treatment until after cycle 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Urinary Survivin Levels	Baseline, week 6 and week 12
Urinary Cytogenitics	baseline and week 12
Progression Free Survival	from first treatment until time of progression or death, whichever comes first
Median Overall Surivial	from first treatment until death
Percentage of Planned Dose Received	from first treatment until end of week 12
Rate of Post-operative Complications	from first treatment until up to 48 hours after surgery.

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Study Chair: Andrew S. Kraft, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2005
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: December 20, 2005
• First Submitted That Met QC Criteria: December 20, 2005
• First Posted (Estimate): December 22, 2005

Study Record Updates

• Last Update Posted (Actual): July 12, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: stage III bladder cancer; recurrent bladder cancer; transitional cell carcinoma of the bladder; stage II bladder cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Paclitaxel; Cisplatin; Bevacizumab
• Other Study ID Numbers: CDR0000454937; MUSC-AVF-3312; MUSC-HR-15537; GENENTECH-AVF-3312; MUSC-CTO-100892