Pazopanib in Treating Patients With Metastatic Urothelial Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00471536
First received: May 8, 2007
Last updated: May 22, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: pazopanib hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The distribution of survival times will be estimated using the Kaplan-Meier method.


Enrollment: 19
Study Start Date: August 2008
Study Completion Date: December 2013
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: pazopanib hydrochloride
800 mg Given orally
Other Names:
  • GW786034B
  • Votrient

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471536

Locations
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Cox Medical Center
Springfield, Missouri, United States, 65807
China, Hong Kong
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, China, OX1 3UJ
Korea, Republic of
Gangnam Severance Hospital
Seoul, Korea, Republic of, 120-752
Sponsors and Collaborators
Investigators
Principal Investigator: Ulka Vaishampayan Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00471536     History of Changes
Other Study ID Numbers: NCI-2009-00203, NCI-2009-00203, CDR0000543460, MAYO-MC0553, MC0553, 7661, N01CM62205
Study First Received: May 8, 2007
Results First Received: February 13, 2013
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urethral Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases

ClinicalTrials.gov processed this record on October 01, 2014