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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00942331
Recruitment Status : Active, not recruiting
First Posted : July 20, 2009
Results First Posted : February 17, 2020
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE July 17, 2009
First Posted Date  ICMJE July 20, 2009
Results First Submitted Date  ICMJE January 30, 2020
Results First Posted Date  ICMJE February 17, 2020
Last Update Posted Date May 14, 2020
Actual Study Start Date  ICMJE July 15, 2009
Actual Primary Completion Date November 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2020)
Overall Survival (OS) [ Time Frame: From date of randomization to date of death due to any cause, assessed up to 7 years ]
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2009)
Overall survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2020)
  • 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 ]
    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 [ Time Frame: Up to 7 years ]
    Objective response rate will be defined as confirmed complete and partial responses using Response Evaluation Criteria in Solid Tumors criteria. 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]).
  • Number of Patients Experiencing Grade 3+ Toxicity [ Time Frame: Up to 7 years ]
    The number of patients experiencing grade 3 or higher toxicity (adverse events considered at least possibly related to treatment) is reported below.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2009)
  • Progression-free survival
  • Objective response rate (complete and partial response)
  • Toxicity
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
Official Title  ICMJE A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients With Advanced Transitional Cell Carcinoma
Brief 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. Immunotherapy with bevacizumab, may induce changes in body's immune system and 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.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine if patients with advanced transitional cell carcinoma treated with bevacizumab, gemcitabine hydrochloride (gemcitabine) 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 arms.

ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, cisplatin IV, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles 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 cycles 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Urothelial Carcinoma
  • Metastatic Bladder Urothelial Carcinoma
  • Metastatic Prostate Carcinoma
  • Metastatic Renal Pelvis Urothelial Carcinoma
  • Metastatic Ureter Urothelial Carcinoma
  • Metastatic Urethral Urothelial Carcinoma
  • Metastatic Urothelial Carcinoma
  • Stage IV Bladder Urothelial Carcinoma AJCC v7
  • Stage IV Prostate Cancer AJCC v7
  • Stage IV Renal Pelvis Cancer AJCC v7
  • Stage IV Ureter Cancer AJCC v7
  • Stage IV Urethral Cancer AJCC v7
  • Unresectable Urothelial Carcinoma
Intervention  ICMJE
  • Biological: Bevacizumab
    Given IV
    Other Names:
    • Anti-VEGF
    • Anti-VEGF Humanized Monoclonal Antibody
    • Anti-VEGF rhuMAb
    • Avastin
    • Bevacizumab awwb
    • Bevacizumab Biosimilar BEVZ92
    • Bevacizumab Biosimilar BI 695502
    • Bevacizumab Biosimilar CBT 124
    • Bevacizumab Biosimilar CT-P16
    • Bevacizumab Biosimilar FKB238
    • Bevacizumab Biosimilar HD204
    • Bevacizumab Biosimilar HLX04
    • Bevacizumab Biosimilar IBI305
    • Bevacizumab Biosimilar LY01008
    • Bevacizumab Biosimilar MIL60
    • Bevacizumab Biosimilar QL 1101
    • Bevacizumab Biosimilar RPH-001
    • Bevacizumab Biosimilar SCT501
    • BP102
    • BP102 Biosimilar
    • HD204
    • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
    • Recombinant Humanized Anti-VEGF Monoclonal Antibody
    • rhuMab-VEGF
    • SCT501
  • Drug: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone''s Chloride
    • Peyrone''s Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other Names:
    • dFdCyd
    • Difluorodeoxycytidine Hydrochloride
    • FF 10832
    • FF-10832
    • FF10832
    • Gemcitabine HCI
    • Gemzar
    • LY-188011
    • LY188011
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Placebo Administration
    Given IV
Study Arms  ICMJE
  • Active Comparator: Arm I (gemcitabine hydrochloride, cisplatin, placebo)
    Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles 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: Cisplatin
    • Drug: Gemcitabine Hydrochloride
    • Other: Laboratory Biomarker Analysis
    • Other: Placebo Administration
  • 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 cycles 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:
    • Biological: Bevacizumab
    • Drug: Cisplatin
    • Drug: Gemcitabine Hydrochloride
    • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 26, 2019)
506
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2009)
500
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date November 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00942331
Other Study ID Numbers  ICMJE NCI-2011-01952
NCI-2011-01952 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000649174
CALGB-90601 ( Other Identifier: Alliance for Clinical Trials in Oncology )
CALGB-90601 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jonathan E Rosenberg Alliance for Clinical Trials in Oncology
PRS Account National Cancer Institute (NCI)
Verification Date March 2020

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