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Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme
This study is not yet open for participant recruitment.
Verified by National Cancer Institute (NCI), April 2009
First Received: May 1, 2009   No Changes Posted
Sponsors and Collaborators: North Central Cancer Treatment Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00892177
  Purpose

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also block the growth of the tumor by blocking blood flow to the tumor. Giving dasatinib together with bevacizumab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of dasatinib when given together with bevacizumab and to see how well it works in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Biological: bevacizumab
Drug: dasatinib
Genetic: fluorescence in situ hybridization
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Procedure: quality-of-life assessment
Phase I
Phase II

MedlinePlus related topics: Cancer
Drug Information available for: Bevacizumab Dasatinib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I/II Study of Dasatinib/Bevacizumab in Recurrent Glioblastoma

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

Primary Outcome Measures:
  • Adverse event profile (Phase I) [ Designated as safety issue: Yes ]
  • Toxicity profile (Phase I) [ Designated as safety issue: Yes ]
  • Response (Phase I) [ Designated as safety issue: No ]
  • Time to treatment-related toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Time to treatment-related grade 3+ toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Time to progression (Phase I) [ Designated as safety issue: No ]
  • Overall survival (Phase I) [ Designated as safety issue: No ]
  • Time to treatment failure (Phase I) [ Designated as safety issue: No ]
  • Progression-free survival at 6 months (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to disease progression (Phase II) [ Designated as safety issue: No ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]
  • Objective response (Phase II) [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v3.0 (Phase II) [ Designated as safety issue: Yes ]

Estimated Enrollment: 95
Study Start Date: May 2009
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of dasatinib in combination with bevacizumab in patients with recurrent or progressive high-grade glioma or glioblastoma multiforme. (Phase I)
  • Assess the safety and adverse events of this regimen in these patients. (Phase I)
  • Estimate the efficacy of this regimen in these patients as measured by 6-month progression-free survival. (Phase II)

Secondary

  • Describe the overall toxicity associated with this regimen in these patients. (Phase I)
  • Describe any preliminary evidence of antitumor activity. (Phase I)
  • Assess the utility of dynamic contrast-enhanced MRI as a predictor of response to this regimen. (Phase II)
  • Determine the relationship between tumor biomarkers and clinical outcome of patients treated with this regimen. (Phase II)
  • Assess the impact of this regimen on the patient's quality of life using FACT-Br. (Phase II)
  • Assess the time to disease progression. (Phase II)
  • Assess the safety and toxicity of this regimen in this patient population. (Phase II)
  • Bank leftover tissue for future NCCTG studies. (Phase II)

OUTLINE: This is a multicenter, dose-escalation study of dasatinib. Patients are stratified according to ECOG performance status (0 vs 1 vs 2), and phase I dose levels (-1 vs 0 vs 1 vs 2 vs 3 or Alt 1 vs Alt 2).

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral dasatinib twice daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed by FACT-Br questionnaire at baseline and prior to every other course. Tissue samples are collected at baseline for biomarker studies and assessed by IHC, RT-PCR, and FISH. Patients undergo dynamic contrast-enhanced MRI at baseline, day 3 of course 1, and day 1 of course 2.

After completion of study therapy, patients are followed periodically for up to 3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas (Phase I)
    • Glioblastoma* multiforme (grade 4 astrocytoma) (Phase II) NOTE: *Variant gliosarcomas are allowed
  • Evidence of tumor recurrence or progression by MRI or CT scan following radiotherapy or most recent antitumor therapy
  • Bidimensionally measurable or evaluable disease by MRI or CT scan
  • No known pleural or pericardial effusion of any grade

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 3 times ULN
  • Creatinine normal
  • Urine protein:creatinine ratio < 1 or urine protein < 1,000 mg on 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • Able to complete questionnaires with or without assistance
  • Willing to return to NCCTG enrolling institution for follow-up
  • Willing to provide mandatory tissue samples for research purposes
  • QTc interval ≤ 450 msec
  • No congenital long QT syndrome
  • No uncontrolled hypertension (systolic BP of > 150 mm Hg or diastolic BP > 100 mm Hg on antihypertensive medications)

    • Well-controlled hypertension allowed
  • No myocardial infarction or unstable angina within the past 6 months
  • No NYHA class II-IV congestive heart failure
  • No significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within the past 6 months
  • No history of any clinically significant ventricular arrhythmias (i.e., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
  • No stroke or transient ischemic attack within the past 6 months
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No evidence of any CNS hemorrhage on baseline CT or MRI
  • No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No immunocompromised patients (other than that related to the use of corticosteroids)

    • Known HIV positivity without clinical evidence of an immunocompromised state allowed
  • No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or prior surgical procedures affecting absorption) that impairs ability to swallow pills
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation)
  • No active or recent history of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situations that would limit compliance with study requirements
  • No other active malignancy within the past 3 years except for nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No known hypersensitivity to any of the components of dasatinib or bevacizumab
  • No significant traumatic injury within the past 28 days
  • No serious nonhealing wounds, ulcers, or bone fractures
  • No hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration

PRIOR CONCURRENT THERAPY:

  • Any number of prior chemotherapy regimens for recurrent disease allowed (Phase I)
  • No more than 2 prior chemotherapy regimens with ≤ 1 regimen for recurrent disease (Phase II)
  • No prior bevacizumab
  • No prior intratumoral therapy, stereotactic radiosurgery, or interstitial brachytherapy except for the following:

    • Separate lesion on MRI that is not part of the previous treatment field
    • Evidence of recurrent disease based on biopsy, MRI spectroscopy, or PET scan
  • At least 7 days since prior core biopsy or other minor surgical procedures (placement of a vascular access device is allowed)
  • At least 7 days since prior drugs that have a risk of causing Torsades de Pointes, including any of the following:

    • Quinidine, procainamide, disopyramide
    • Amiodarone, sotalol, ibutilide, dofetilide
    • Erythromycin, clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
  • At least 28 days since prior and no concurrent major surgical procedure or open biopsy
  • At least 12 weeks since prior radiotherapy
  • No concurrent therapeutic anticoagulation with warfarin, except low-dose warfarin for venous or arterial access devices, provided INR < 1.5

    • Therapeutic anticoagulation with low molecular weight heparin allowed
  • No other concurrent investigational agent considered as a therapy for the primary neoplasm
  • No concurrent therapy (other than hormonal therapy) for other prior malignancy
  • No concurrent H_2 blockers or proton pump inhibitors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892177

Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Evanthia Galanis, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000641746, NCCTG-N0872
Study First Received: May 1, 2009
Last Updated: May 1, 2009
ClinicalTrials.gov Identifier: NCT00892177     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
adult mixed glioma
recurrent adult brain tumor
adult anaplastic oligodendroglioma
adult oligodendroglioma
adult anaplastic astrocytoma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Bevacizumab
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Angiogenesis Inhibitors
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Dasatinib
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Oligodendroglioma
Glioma
Glioblastoma Multiforme
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Glioblastoma
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Central Nervous System Neoplasms
Bevacizumab
Protein Kinase Inhibitors
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Dasatinib
Therapeutic Uses
Glioma
Angiogenesis Modulating Agents
Growth Inhibitors
Nervous System Neoplasms
Neoplasms by Histologic Type
Astrocytoma
Growth Substances
Nervous System Diseases
Enzyme Inhibitors
Angiogenesis Inhibitors
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009