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

January 16, 2007
December 6, 2013
January 2007
March 2011   (final data collection date for primary outcome measure)
Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Objective response (partial response [PR] or complete response [CR]) OR 6-month progression-free survival (PFS)
Complete list of historical versions of study NCT00423735 on ClinicalTrials.gov Archive Site
  • 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.
  • Six-month PFS rate
  • Overall survival distribution
  • Treatment adverse events
  • Objective response rates (CR, PR, stable disease, disease progression) as measured by RECIST criteria
  • PFS distribution
  • Molecular correlates of clinical outcome
Not Provided
Not Provided
 
Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Phase II Trial of Dasatinib in Patients With Recurrent Glioblastoma Multiforme

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
Drug: dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel
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
Intervention: Drug: dasatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
113
Not Provided
March 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00423735
NCI-2009-00744, NCI-2009-00744, CDR0000526070, RTOG 0627, RTOG-0627, U10CA021661
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Andrew Lassman Radiation Therapy Oncology Group
National Cancer Institute (NCI)
December 2013

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