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Pazopanib in Treating Patients With Metastatic Urothelial Cancer

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ClinicalTrials.gov Identifier: NCT00471536
Recruitment Status : Completed
First Posted : May 10, 2007
Results First Posted : March 21, 2013
Last Update Posted : May 30, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 8, 2007
First Posted Date  ICMJE May 10, 2007
Results First Submitted Date  ICMJE February 13, 2013
Results First Posted Date  ICMJE March 21, 2013
Last Update Posted Date May 30, 2014
Study Start Date  ICMJE August 2008
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2013)
Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST]) [ Time Frame: Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment. ]
Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. Per RECIST v1.0 criteria: A Complete Response (CR) requires the disappearance of all target lesions. A Partial Response (PR) requires >=30% decrease in the sum of the longest diameter of target lesions from baseline measurement. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.
Original Primary Outcome Measures  ICMJE
 (submitted: May 8, 2007)
Tumor response rate (complete and partial)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2013)
  • Adverse Events Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: Every 4 weeks during treatment (maximum duration was 44 weeks) ]
    The maximum grade for each adverse event considered to be at least possibly related to treatment will be recorded. Frequency tables will be constructed.
  • Confirmed Tumor Response (CR and PR) [ Time Frame: Documented on 2 consecutive evaluations 8 weeks apart from the start of the treatment until disease progression/recurrence, assessed up to 1 year ]
    Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. A confirmed response is defined as a CR or PR and is documented on 2 consecutive evaluations.
  • Duration of Response [ Time Frame: From the time an objective response is first noted to be either a CR or PR to the date progression is documented, assessed up to 1 year ]
    The distribution of response durations will be estimated using the Kaplan-Meier method.
  • Time to Disease Progression [ Time Frame: Every 3 months from registration until progressive disease (PD), assessed up to 2 years after registration ]
    The distribution of progression-free survival times will be estimated using the Kaplan-Meier method.
  • Survival Time [ Time Frame: Time from registration until death due to any cause, assessed every 6 months after PD for up to 2 years after registration ]
    The distribution of survival times will be estimated using the Kaplan-Meier method.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2007)
  • Adverse events
  • Confirmed tumor response (complete and partial)
  • Duration of Response
  • Time to Disease Progression
  • Survival Time
  • Serum vascular endothelial growth factor (VEGF) levels
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pazopanib in Treating Patients With Metastatic Urothelial Cancer
Official Title  ICMJE A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer
Brief Summary This phase II trial is studying the side effects and how well pazopanib works in treating patients with metastatic urothelial cancer. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Detailed Description

PRIMARY OBJECTIVES:

I. Assess the anti tumor activity and toxicity profile of pazopanib hydrochloride in patients with metastatic urothelial cancer.

SECONDARY OBJECTIVES:

I. Evaluate the pharmacokinetics of pazopanib hydrochloride in these patients. II. Evaluate pre- and post-treatment changes in circulating endothelial cells, monocytes and platelets, and angiogenesis-related factors in these patients.

OUTLINE: This is a multicenter study. Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically for correlative studies and pharmacological studies. Samples are analyzed for vascular endothelial growth factor (VEGF) and soluble VEGF receptor II concentration via ELISA. Circulating endothelial cells are also measured.

After completion of study treatment, patients are followed for 1 year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Distal Urethral Cancer
  • Proximal Urethral Cancer
  • Recurrent Bladder Cancer
  • Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Recurrent Urethral Cancer
  • Stage IV Bladder Cancer
  • Transitional Cell Carcinoma of the Bladder
  • Urethral Cancer Associated With Invasive Bladder Cancer
Intervention  ICMJE Drug: pazopanib hydrochloride
800 mg Given orally
Other Names:
  • GW786034B
  • Votrient
Study Arms  ICMJE Experimental: Treatment (enzyme inhibitor therapy)
Patients receive 800 mg oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: pazopanib hydrochloride
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 Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2013)
19
Original Enrollment  ICMJE
 (submitted: May 8, 2007)
32
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed transitional cell cancer of the urothelium or bladder

    • Metastatic disease
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
  • No known brain metastases
  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • PT/INR/PTT ≤ 1.2 times ULN
  • No proteinuria > 1+ on two consecutive dipsticks measured ≥ 1 week apart
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study
  • No condition that impairs the ability to swallow and retain pazopanib hydrochloride tablets, including any of the following:

    • Gastrointestinal tract disease resulting in an inability to take oral medication
    • Requirement for IV alimentation
    • Prior surgical procedures affecting absorption
    • Active peptic ulcer disease
  • No uncontrolled illness that would limit compliance with study therapy including, but not limited to, any of the following:

    • Ongoing or active infection
    • Psychiatric illness or social situations
  • No QTc prolongation (defined as a QTc interval ≥ 480 msecs) or other significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia)
  • No other conditions, including any of the following:

    • Serious or non-healing wound, ulcer, or bone fracture
    • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
    • Cerebrovascular accident within the past 6 months
    • Myocardial infarction, cardiac arrhythmia, or admission for unstable angina within the past 12 weeks
    • Venous thrombosis within the past 12 weeks
    • New York Heart Association (NYHA) class III or IV heart failure

      • Asymptomatic NYHA class II heart failure on treatment allowed
  • No other active second malignancy other than non-melanoma skin cancer

    • Patients are not considered to have an active malignancy if they have completed anti-cancer therapy and are considered by their physician to be ≤ 30% risk of relapse
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • At least 4 weeks since prior radiotherapy
  • Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1 measurable and/or evaluable lesion(s) that has not been irradiated
  • At least 4 weeks since prior surgery
  • One prior chemotherapy regimen for metastatic urothelial or bladder cancer
  • More than 12 weeks since prior cardiac angioplasty or stenting
  • Prior adjuvant or neoadjuvant therapy allowed
  • No prior experimental treatment for metastatic disease
  • No other prior or concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent CYP2C9 substrates, including any of the following:

    • Anticoagulants (e.g., warfarin [therapeutic doses only])

      • Low molecular weight heparin and prophylactic low-dose warfarin (≤ 2 mg daily) allowed
    • Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or nateglinide)
    • Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or methylergonovine)
    • Antipsychotics (e.g., pimozide or clozapine)
    • Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)
    • Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexiletine, amiodarone, quinidine, or propafenone)
    • Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)
    • Miscellaneous drugs (e.g., theophylline, quetiapine, risperidone, tacrine, or atomoxetine)
  • No other concurrent anticancer agents or therapies
  • No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes
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 China,   Korea, Republic of,   United States
Removed Location Countries Hong Kong,   Taiwan
 
Administrative Information
NCT Number  ICMJE NCT00471536
Other Study ID Numbers  ICMJE NCI-2009-00203
NCI-2009-00203 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000543460
MAYO-MC0553
MC0553 ( Other Identifier: Mayo Clinic )
7661 ( Other Identifier: CTEP )
N01CM62205 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
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: Ulka Vaishampayan Mayo Clinic
PRS Account National Cancer Institute (NCI)
Verification Date December 2013

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