Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00423735
First received: January 16, 2007
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

This phase II trial is studying how well dasatinib works in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: dasatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of patients achieving objective response (partial response [PR] or complete response [CR]) OR 6-month progression-free survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Overall survival distribution [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Rates of treatment adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Objective response rates (CR, PR, stable disease, progression) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • PFS distribution [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.


Estimated Enrollment: 113
Study Start Date: January 2007
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dasatinib)
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Drug: dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the therapeutic efficacy of dasatinib, in terms of 6-month progression-free survival, in all patients (i.e., stage 1B [closed to accrual as of 4/14/2009] and stage 2 [closed to accrual as of 4/14/2009] combined) with recurrent/progressive glioblastoma multiforme or gliosarcoma.

SECONDARY OBJECTIVES:

I. Determine the therapeutic efficacy of this drug, in terms of a hybrid endpoint of 6-month progression-free survival or objective response (complete or partial) rate, in patients in stage 1B (closed to accrual as of 4/14/2009).

II. Determine overall survival of patients treated with this regimen. III. Determine the toxicity of this regimen in these patients. IV. Determine radiographic response rate in patients treated with this regimen. V. Determine progression-free survival of patients treated with this regimen. VI. Explore molecular correlates of clinical outcome in patients treated with this regimen.

VII. Explore pharmacokinetic correlates of dosing, toxicity, and efficacy.

OUTLINE: This a multicenter study.

Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed periodically.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed glioblastoma multiforme or gliosarcoma

    • Pre-therapy tumor tissue available
  • Meets 1 of the following criteria:

    • Patients accrued to stage 1 (closed to accrual as of 4/14/2009) or stage 1B (opened to accrual as of 4/14/2009) must have tumors overexpressing at least 2 known dasatinib targets (i.e., SRC, KIT, PDGFR, or EPHA2)
    • Patients accrued to stage 2 (closed as of 4/14/2009) do not require overexpression of SRC, KIT, PDGFR, or EPHA2
  • Prior treatment with radiotherapy and temozolomide required
  • Radiographic evidence of tumor progression by MRI or CT scan

    • Must be on stable or decreasing doses of corticosteroids for at least 5 days before baseline MRI or CT scan
  • Measurable disease is not required in patients who recently underwent resection provided the following conditions are met as applicable:

    • Progression of disease necessitated surgery
    • Polifeprosan 20 with carmustine implants (Gliadel wafers®) were not placed during the most recent surgery
    • Neither convection-enhanced delivery nor catheters for infusion of chemotherapy were used during the most recent surgery
    • Radioactive seeds were not placed during the most recent surgery
    • The histology of the most recent surgery documented recurrent/persistent/progressive malignant glioma
  • Karnofsky performance status 60-100%
  • Absolute neutrophil count ≥ 1,000 cells/mm³
  • Platelet count ≥ 75,000 cells/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
  • WBC ≥ 3,000 cells/mm³
  • Absolute lymphocyte count ≥ 500 cells/mm³
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine ≤ 3 times ULN OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior invasive malignancy except for nonmelanomatous skin cancer unless disease-free for a minimum of 3 years
  • No severe active comorbidity, defined as any of the following:

    • Clinically significant cardiovascular disease, including any of the following:

      • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
      • Transmural myocardial infarction or ventricular tachyarrhythmia within the past 6 months
      • Prolonged QTc > 480 msec (by Fridericia's correction)
      • Ejection fraction less than institutional normal
      • Major conduction abnormality (unless a cardiac pacemaker is present)
    • Acute bacterial or fungal infection requiring IV antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization
  • No known AIDS
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to dasatinib
  • No condition that impairs the ability to swallow or retain tablets, such as the following:

    • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
    • Prior surgical procedures affecting absorption
    • Active peptic ulcer disease
  • No other concurrent anticancer agents or therapies
  • Prior surgery for recurrent/progressive disease allowed

    • Recovered from prior surgery
  • More than 4 weeks since prior radiotherapy and recovered
  • More than 2 weeks since prior temozolomide and recovered
  • More than 2 weeks since prior and no concurrent enzyme-inducing antiepileptic drugs
  • No prior therapy except radiotherapy and temozolomide
  • No prior stereotactic radiosurgery or brachytherapy
  • At least 7 days since prior and no concurrent potent inhibitors of CYP3A4
  • At least 7 days since prior and no concurrent agents with proarrhythmic potential
  • At least 7 days since prior and no concurrent antithrombotic and/or antiplatelet agents (e.g., warfarin, heparin, low molecular weight heparin, acetylsalicylic acid, clopidogrel, ticlopidine, or Aggrenox)
  • No locally acting antacids (Maalox, Mylanta) within 2 hours before or after study treatment
  • No concurrent systemic antacids, including H2 receptor antagonist or proton pump inhibitors
  • No concurrent ibuprofen or NSAIDs
  • No concurrent large quantities of grapefruit or its juice
  • No concurrent potent inducers of CYP3A4
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423735

  Show 129 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Andrew Lassman Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00423735     History of Changes
Other Study ID Numbers: NCI-2009-00744, NCI-2009-00744, CDR0000526070, RTOG 0627, RTOG-0627, U10CA021661
Study First Received: January 16, 2007
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Gliosarcoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014