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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00942331
First received: July 17, 2009
Last updated: September 16, 2014
Last verified: August 2014

July 17, 2009
September 16, 2014
July 2009
June 2019   (final data collection date for primary outcome measure)
Overall survival (OS) [ Time Frame: From date of randomization to date of death due to any cause, assessed up to 7 years ] [ Designated as safety issue: No ]
The Kaplan- Meier product-limit estimator will be used to estimate the OS. The stratified log-rank statistic will be the primary analysis to compare the two treatment arms on OS with the stratification factors: presence of visceral metastases (no, yes) and prior chemotherapy (no, yes). In addition, the proportional hazards model will be used to assess the importance of the treatment arm adjusting on patient characteristics, stratification variables and other important covariates in predicting OS.
Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00942331 on ClinicalTrials.gov Archive Site
  • Progression-free survival (PFS) [ Time Frame: From the date of randomization to date of progression or death due to any cause, whichever occurs first, assessed up to 7 years ] [ Designated as safety issue: No ]
    The primary analysis of PFS will be a two-sided stratified log-rank test comparing arm A and arm B. The stratification factors will consist of the two stratification factors used for patient randomization: prior nephrectomy (yes vs. no) and Motzer score (0 vs. 1−2 vs. 3+). Results from unstratified log-rank tests will also be provided. Kaplan-Meier methodology will be used to estimate median PFS for each treatment arm.
  • Objective response rate (defined as confirmed complete and partial responses) using Response Evaluation Criteria in Solid Tumors criteria [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    The Cochran-Mantel-Haenszel test will be used to compare the two arms on the proportion of patients who experience an objective response adjusting on the stratification factors (presence of visceral disease [no, yes] and prior chemotherapy [no, yes]).
  • Grade 3 or greater treatment-related toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    The Fisher exact test will be used to compare the two treatment arms on the proportion of patients with unacceptable treatment related grade 3 or higher toxicity.
  • Progression-free survival [ Designated as safety issue: No ]
  • Objective response rate (complete and partial response) [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients With Advanced Transitional Cell Carcinoma

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 together with or without bevacizumab in treating patients with urinary tract cancer.

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 and 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Distal Urethral Cancer
  • Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Proximal Urethral Cancer
  • Recurrent Bladder Cancer
  • Recurrent Prostate Cancer
  • Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Recurrent Urethral Cancer
  • Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Stage IV Bladder Cancer
  • Stage IV Prostate Cancer
  • Stage IV Urethral Cancer
  • Transitional Cell Carcinoma of the Bladder
  • Ureter Cancer
  • Urethral Cancer Associated With Invasive Bladder Cancer
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
    • dFdC
    • difluorodeoxycytidine hydrochloride
    • gemcitabine
    • Gemzar
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Other: placebo
    Given IV
    Other Name: PLCB
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Other: laboratory biomarker analysis
    Correlative studies
  • Active Comparator: Arm I (gemcitabine hydrochloride, cisplatin, placebo)
    Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 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.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Drug: cisplatin
    • Other: placebo
    • Other: laboratory biomarker analysis
  • Experimental: Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
    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.
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Drug: cisplatin
    • Biological: bevacizumab
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
Not Provided
June 2019   (final data collection date for primary outcome measure)

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
  • Patients may not have received prior 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 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 > 35mIU/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
Both
18 Years and older
No
United States,   Puerto Rico
 
NCT00942331
NCI-2011-01952, NCI-2011-01952, CALGB 90601, CDR0000649174, CALGB 90601, CALGB-90601, U10CA180821, U10CA031946
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jonathan Rosenberg Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP