Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosed18 and overNCINCI-2011-01952
CDR0000649174, CALGB 90601, U10CA180821, U10CA031946, NCT00942331

Trial Description

Summary

This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine if patients with advanced transitional cell carcinoma treated with bevacizumab, gemcitabine (gemcitabine hydrochloride) and cisplatin will have increased overall survival when compared to patients treated with gemcitabine, cisplatin, and placebo.

SECONDARY OBJECTIVES:

I. To compare the progression-free survival of these two regimens in patients with advanced transitional cell carcinoma.

II. To compare the proportion of patients who experience an objective response on each regimen.

III. To compare the grade 3 and greater toxicities in patients treated on the two regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, cisplatin IV over 1 hour, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 7 years.

Eligibility Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically documented metastatic or unresectable transitional cell (urothelial) carcinoma of the urinary tract (renal pelvis, ureter, bladder, prostate, or urethra), with metastatic or locally advanced disease (T4b, N2, N3, or M1); patients must not be candidates for potentially curative surgery or radiotherapy
  • For patients that have had surgical resection prior to study enrollment, residual or unresected disease (measurable and/or unmeasurable) must be evident on post-surgical scans
  • Prior treatment for transitional cell carcinoma (TCC)
  • Patients may not have received combination systemic chemotherapy for metastatic disease
  • For the purposes of this study, radiosensitizing single agent chemotherapy is not considered prior systemic therapy
  • Prior neoadjuvant or adjuvant systemic chemotherapy is permissible provided the interval from end of therapy to diagnosis of metastatic disease is at least 1 year
  • >= 4 weeks since any prior radiation (including palliative) or major surgery and fully recovered
  • >= 7 days since any minor surgery such as port placement
  • >= 4 weeks since any intravesical therapy
  • No prior treatment with bevacizumab or other angiogenesis inhibitors
  • No known history of brain metastases; brain imaging (magnetic resonance imaging [MRI]/computed tomography [CT]) is not required
  • No current congestive heart failure; New York Heart Association (NYHA) class II, III or IV
  • Patients with history of hypertension must be well controlled (< 150/90) on a regimen of anti-hypertensive therapy
  • Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range international normalized ratio (INR) (usually between 2 and 3) or be on a stable dose of low molecular weight (LMW) heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible
  • No significant history of bleeding events or gastrointestinal (GI) perforation
  • Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible
  • Patients with a history of GI perforation within 12 months of registration are not eligible
  • Patients with a history of peritoneal carcinomatosis are not eligible
  • No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible
  • Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study
  • No serious or non-healing wound, ulcer, or bone fracture
  • No sensory or motor peripheral neuropathy >= grade 2
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
  • Patients that are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to registration
  • For women of child-bearing potential with an elevated beta-HCG that is believed to be related to cancer and not pregnancy, a negative trans-vaginal ultrasound and gynecological examination are required
  • Women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL); even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (or Karnofsky performance status [KPS] >= 80)
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Calculated or measured creatinine clearance >= 50 mL/minute
  • Bilirubin =< 1.25 times upper limits of normal; for patients with Gilbert's disease, =< 2.5 x upper limit of normal (ULN) is allowed
  • Aspartate aminotransferase (AST) =< 2.0 x upper limits of normal
  • Urine protein to creatinine ratio < 1.0 or urine protein =< 1+ or 24-hour urine protein =< 1 gram

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

    Jonathan Rosenberg, Principal Investigator

    Trial Sites

    U.S.A.

    Alabama
    Birmingham

    UAB Comprehensive Cancer Center

    Carla I. Falkson
    Ph: 205-934-0309

    Colorado
    Alamosa

    San Luis Valley Regional Medical Center

    Thomas W Flaig
    Ph: 720-848-0650

    Aurora

    University of Colorado Cancer Center at UC Health Sciences Center

    Thomas W Flaig
    Ph: 720-848-0650

    Denver

    University of Colorado Cancer Center at UC Health Sciences Center

    Jonathan Rosenberg
    Ph: 212-639-7202
    Email: rosenbj1@mskcc.org

    Georgia
    Atlanta

    CCOP - Atlanta Regional

    Thomas E. Seay
    Ph: 404-303-3355

    Northside Hospital Cancer Center

    Thomas E. Seay
    Ph: 404-303-3355

    Piedmont Hospital

    Thomas E. Seay
    Ph: 404-303-3355

    Saint Joseph's Hospital of Atlanta

    Thomas E. Seay
    Ph: 404-303-3355

    Austell

    WellStar Cobb Hospital

    Thomas E. Seay
    Ph: 404-303-3355

    Columbus

    John B. Amos Cancer Center

    Thomas E. Seay
    Ph: 404-303-3355

    Decatur

    Charles B. Eberhart Cancer Center at DeKalb Medical Center

    Thomas E. Seay
    Ph: 404-303-3355

    Fayetteville

    Piedmont Fayette Hospital

    Thomas E. Seay
    Ph: 404-303-3355

    Lawrenceville

    Gwinnett Medical Center

    Thomas E. Seay
    Ph: 404-303-3355

    Marietta

    Kennestone Cancer Center at Wellstar Kennestone Hospital

    Thomas E. Seay
    Ph: 404-303-3355

    Riverdale

    Southern Regional Medical Center

    Thomas E. Seay
    Ph: 404-303-3355

    Illinois
    Galesburg

    Medical and Surgical Specialists, LLC

    Nguyet A Le-Lindqwister
    Ph: 800-793-2262

    Massachusetts
    Springfield

    Baystate Medical Center

    Leslie Marion Howard
    Ph: 413-794-3565
    Email: tamara.wrenn@baystatehealth.org

    Minnesota
    Fergus Falls

    Lake Region Healthcare Corporation-Cancer Care

    Preston D. Steen
    Ph: 701-234-6161

    North Carolina
    High Point

    High Point Regional Hospital

    George H Sanders
    Ph: 336-878-6107

    North Dakota
    Bismarck

    Bismarck Cancer Center

    John T Reynolds
    Ph: 701-323-5760
    Email: tfischer@mohs.org

    South Carolina
    Anderson

    AnMed Cancer Center

    Charles E Bowers
    Ph: 800-486-5941

    Virginia
    Richmond

    Virginia Commonwealth University Massey Cancer Center

    John D. Roberts
    Ph: 804-628-1939

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT00942331
    ClinicalTrials.gov processed this data on May 20, 2015

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.