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Pazopanib in Treating Patients With Recurrent Glioblastoma
This study has been completed.
First Received: April 9, 2007   Last Updated: April 14, 2009   History of Changes
Sponsors and Collaborators: North American Brain Tumor Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00459381
  Purpose

RATIONALE: 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.

PURPOSE: This phase II trial is studying the side effects and how well pazopanib works in treating patients with recurrent glioblastoma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: pazopanib hydrochloride
Phase II

MedlinePlus related topics: Cancer
Drug Information available for: Pazopanib Pazopanib Hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Trial of GW786034 (Pazopanib) in Patients With Recurrent Glioblastoma

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

Primary Outcome Measures:
  • 6-month progression-free survival [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Radiographic response [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: May 2007
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the therapeutic efficacy of pazopanib hydrochloride, as measured by 6-month progression-free survival (PFS), in patients with recurrent glioblastoma .
  • Determine the safety profile of this drug in these patients.

Secondary

  • Determine the efficacy of this drug, as measured by radiographic response, time to progression, and overall survival, in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 2 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme, including gliosarcoma

    • Recurrent disease
  • Must have unequivocal radiographic evidence of tumor progression by MRI, as defined by any of the following:

    • 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline
    • Clear worsening of any evaluable disease
    • Appearance of any new lesions or site
    • Clear clinical worsening
  • Must have failed prior radiotherapy that was completed ≥ 42 days ago
  • Patients who received prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease, rather than radiation necrosis, based on positron emission tomography (PET) scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation of disease
  • Treatment for no more than 2 prior relapses allowed

    • Relapse is defined as progression following initial therapy (i.e., radiotherapy with or without chemotherapy, if that was used as initial therapy; therefore no more than 3 prior therapies [initial therapy and therapy for 2 relapses] allowed)

      • If the patient had a surgical resection for relapsed disease and no anticancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse
      • For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a glioblastoma multiforme will be considered the first relapse

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin ≥ 10 g/dL (may be reached by transfusion)
  • Platelet count ≥ 100,000/mm^3
  • PT/INR/PTT ≤ 1.2 times upper limit of normal (ULN)
  • SGOT < 2.5 times ULN
  • Bilirubin < 2.5 times ULN
  • Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
  • Urine protein:creatinine ratio > 1 OR urine protein < 1,000 mg by 24-hour urine collection OR proteinuria < 1+
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-barrier contraception during study therapy OR practice abstinence from sexual intercourse for 14 days prior to, during, and for ≥ 21 days after study therapy
  • Systolic blood pressure (BP) ≤ 140 mm Hg and diastolic BP ≤ 90 mm Hg

    • Prior initiation or adjustment of BP medication allowed provided the average of 3 BP readings is ≤ 140/90 mm Hg
  • No uncontrolled significant medical illnesses that would preclude study therapy
  • No other conditions, including any of the following:

    • Serious or nonhealing wound, ulcer, or bone fracture
    • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
    • Cerebrovascular accident (CVA) within the past 6 months
    • Myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty, or stenting within the past 84 days
    • Venous thrombosis within the past 84 days
    • New York Heart Association (NYHA) class III or IV heart failure

      • Asymptomatic NYHA class II heart failure while on treatment allowed
  • No other cancer except for nonmelanoma skin cancer or carcinoma in situ of the cervix unless in complete remission and off of all therapy for that disease for ≥ 3 years
  • No disease that would obscure toxicity or dangerously alter drug metabolism
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents
  • No QTc prolongation (i.e., QTc interval ≥ 500 msecs) or other significant ECG abnormalities
  • No condition that impairs the ability to swallow and retain pazopanib hydrochloride, 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 28 days since prior resection of recurrent or progressive tumor and recovered

    • Residual disease after resection of recurrent glioblastoma is not mandated for eligibility into the study
  • More than 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin)

    • Radiosensitizers allowed
  • More than 14 days since prior investigational agents
  • More than 14 days since prior vincristine
  • More than 21 days since prior procarbazine
  • More than 28 days since prior cytotoxic therapy
  • More than 42 days since prior nitrosoureas
  • No prior bevacizumab
  • No prior sorafenib tosylate or sunitinib malate
  • No prior pazopanib hydrochloride
  • No concurrent CYP2C9 substrates, including any of the following:

    • Anticoagulants (e.g., warfarin [therapeutic doses only])
    • Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or nateglinide)
    • Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or methylergonovine)
    • Neuroleptics (e.g., pimozide)
    • Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)
    • Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexilitine, amiodarone, quinidine, or propafenone)
    • Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)
    • Miscellaneous drugs (e.g., theophylline, quetiapine, risperidone, tacrine, clozapine, or atomoxetine)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal treatment, or immunotherapy) or investigational drugs
  • No concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)

    • Non-EIAEDs allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00459381

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan - Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
North American Brain Tumor Consortium
Investigators
Study Chair: Howard A. Fine, MD NCI - Neuro-Oncology Branch
  More Information

Additional Information:
No publications provided

Responsible Party: North American Brain Tumor Consortium ( Michael Prados )
Study ID Numbers: CDR0000538083, NABTC-0602, NCI-07-C-0138
Study First Received: April 9, 2007
Last Updated: April 14, 2009
ClinicalTrials.gov Identifier: NCT00459381     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult giant cell glioblastoma
adult gliosarcoma
recurrent adult brain tumor
adult glioblastoma

Study placed in the following topic categories:
Neuroectodermal Tumors
Brain Neoplasms
Glioblastoma
Astrocytoma
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Glioma
Central Nervous System Neoplasms
Gliosarcoma
Recurrence
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Glioblastoma
Neoplasms by Histologic Type
Astrocytoma
Nervous System Diseases
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Glioma
Neoplasms, Neuroepithelial
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009