This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Pazopanib in Treating Patients With Recurrent Glioblastoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00459381
First received: April 9, 2007
Last updated: January 25, 2017
Last verified: January 2017
  Purpose
This phase II trial is studying the side effects and how well pazopanib works in treating patients with recurrent glioblastoma. 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
Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor Drug: pazopanib hydrochloride Other: laboratory biomarker analysis Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of GW786034 (Pazopanib) in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 6 Months Progression-free Survival [ Time Frame: 6 months ]
    Calculated from study registration till 6month time point. Progression defined by Macdonald criteria Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration

  • Number of Participants Discontinuing Treatment Due to Toxicity [ Time Frame: 2 years ]
    Use NCI Common toxicity Criteria Adverse Event Version 3.0 to grade toxicities. Any patient who received at least one dose of pazopanib was evaluable for toxicity. Calculated the number of participants who had an event that was related to pazopanib that caused the patient to stop treatment due to this event.


Secondary Outcome Measures:
  • Most Common Toxicities Experienced After at Least One Dose of Pazopanib [ Time Frame: Up to 2 years ]
    NCI Common Toxicity Criteria (CTCAE) version 3.0. All patients that received at least one dose of pazopanib were evaluable. All events recorded that were related to drug were calculated per patient.

  • Overall Radiographic Response (ORR) Rate [ Time Frame: 2 years ]

    The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features

    1: complete response; 2: partial response; 3:stable disease; 4:progression

    Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved

    Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved

    Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable

    Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration


  • Best Radiographic Response [ Time Frame: 3 years ]

    Using the Macdonald criteria, the best MRI image response while the patient was on active treatment.

    1: complete response; 2: partial response; 3:stable disease; 4:progression

    Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved

    Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved

    Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable

    Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration


  • Overall Survival [ Time Frame: From date of registration to date of death due to any cause, assessed up to 2 years ]
    calculated from study registration until date of death or patient censored at the last date known alive

  • Time to Progression or Progression Free Survival [ Time Frame: 1 year ]

    PFS for patients who died on treatment or within 30 days of the end of treatment w/out progression date, was date of death. All other pts without documented progression were censored at the date of last follow-up prior to start new treatment.

    All 35 patients were included in an intent to treat analysis for PFS and OS. 3 pts censored for PFS, all less than 2 wks after study registration.



Enrollment: 35
Study Start Date: May 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)

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

Other: laboratory biomarker analysis

Drug: pazopanib hydrochloride
Given orally
Other Names:
  • GW786034B
  • Votrient
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the therapeutic efficacy of pazopanib hydrochloride, as measured by 6-month progression-free survival (PFS), in patients with recurrent glioblastoma.

II. Determine the safety profile of this drug in these patients.

SECONDARY OBJECTIVES:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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
  • 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
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: NCT00459381

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
University of California San Francisco
San Francisco, California, United States, 94115
United States, Maryland
National Cancer Institute Neuro-Oncology Branch
Bethesda, Maryland, United States, 20814
United States, Massachusetts
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 University
Durham, North Carolina, United States, 27710
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Howard Fine, MD North American Brain Tumor Consortium
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00459381     History of Changes
Other Study ID Numbers: NCI-2012-02710
NABTC-0602
U01CA062399 ( U.S. NIH Grant/Contract )
CDR0000538083 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: April 9, 2007
Results First Received: October 12, 2016
Last Updated: January 25, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

ClinicalTrials.gov processed this record on August 23, 2017