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
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: NCT00423735

  Hide Study Locations
Locations
United States, Alabama
Mobile Infirmary Medical Center
Mobile, Alabama, United States, 36607
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, California
Auburn Radiation Oncology Center
Auburn, California, United States, 95603
Marshall Radiation Oncology Center
Cameron Park, California, United States, 95682
Mercy San Juan Medical Center
Carmichael, California, United States, 95608
Innovative Cancer Research Consortium at Glendale Adventist
Glendale, California, United States, 91206
Roseville Radiation Oncology Center
Roseville, California, United States, 95661
Radiological Associates of Sacramento
Sacramento, California, United States, 95815
Mercy General Hospital Radiation Oncology Center
Sacramento, California, United States, 95819
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Solano Radiation Oncology Center
Vacaville, California, United States, 95687
United States, Connecticut
Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Delaware
Beebe Medical Center
Lewes, Delaware, United States, 19958
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States, 19718
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Bay Medical Center
Panama City, Florida, United States, 32401
United States, Georgia
John B Amos Cancer Center
Columbus, Georgia, United States, 31904
Memorial Health University Medical Center
Savannah, Georgia, United States, 31403
United States, Indiana
IU Health Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Kansas
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Saint Luke's South Hospital
Overland Park, Kansas, United States, 66213
Shawnee Mission Medical Center
Shawnee Mission, Kansas, United States, 66204
United States, Maryland
Union Hospital of Cecil County
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Michigan Cancer Research Consortium Community Clinical Oncology Program
Ann Arbor, Michigan, United States, 48106
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
Oakwood Hospital
Dearborn, Michigan, United States, 48124
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Green Bay Oncology - Escanaba
Escanaba, Michigan, United States, 49431
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States, 48532
Hurley Medical Center
Flint, Michigan, United States, 48502
Green Bay Oncology - Iron Mountain
Iron Mountain, Michigan, United States, 49801
Allegiance Health
Jackson, Michigan, United States, 49201
Sparrow Hospital
Lansing, Michigan, United States, 48912
Saint Mary Mercy Hospital
Livonia, Michigan, United States, 48154
Saint Joseph Mercy Oakland
Pontiac, Michigan, United States, 48341-2985
Saint Joseph Mercy Port Huron
Port Huron, Michigan, United States, 48060
Saint Mary's of Michigan
Saginaw, Michigan, United States, 48601
Saint John Macomb-Oakland Hospital
Warren, Michigan, United States, 48093
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview-Southdale Hospital
Edina, Minnesota, United States, 55435
Unity Hospital
Fridley, Minnesota, United States, 55432
Hutchinson Area Health Care
Hutchinson, Minnesota, United States, 55350
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States, 55109
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
North Memorial Medical Health Center
Robbinsdale, Minnesota, United States, 55422
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States, 55416
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
Regions Hospital
Saint Paul, Minnesota, United States, 55101
United Hospital
Saint Paul, Minnesota, United States, 55102
Saint Francis Regional Medical Center
Shakopee, Minnesota, United States, 55379
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Minnesota Oncology and Hematology PA-Woodbury
Woodbury, Minnesota, United States, 55125
United States, Mississippi
Singing River Hospital
Pascagoula, Mississippi, United States, 39581
United States, Missouri
Cape Radiation Oncology
Cape Girardeau, Missouri, United States, 63703
Centerpoint Medical Center LLC
Independence, Missouri, United States, 64057
North Kansas City Hospital
Kansas City, Missouri, United States, 64116
Saint Luke's Cancer Institute
Kansas City, Missouri, United States, 64111
Research Medical Center
Kansas City, Missouri, United States, 64132
Saint Joseph Health Center
Kansas City, Missouri, United States, 64114
Heartland Hematology and Oncology Associates Incorporated
Kansas City, Missouri, United States, 64118
Truman Medical Center
Kansas City, Missouri, United States, 64108
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States, 64111
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, United States, 64086
Liberty Hospital
Liberty, Missouri, United States, 64068
Liberty Radiation Oncology Clinic
Liberty, Missouri, United States, 64068
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
Springfield, Missouri, United States, 65802
Cox Medical Center
Springfield, Missouri, United States, 65807
United States, New Hampshire
Cheshire Medical Center-Dartmouth-Hitchcock Keene
Keene, New Hampshire, United States, 03431
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Cooper Hospital University Medical Center
Camden, New Jersey, United States, 08103
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
Mount Holly, New Jersey, United States, 08060
Sparta Cancer Treatment Center
Sparta, New Jersey, United States, 07871
Virtua West Jersey Hospital Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Highland Hospital
Rochester, New York, United States, 14620
University of Rochester
Rochester, New York, United States, 14642
United States, Ohio
Akron General Medical Center
Akron, Ohio, United States, 44307
Aultman Health Foundation
Canton, Ohio, United States, 44710
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Samaritan North Health Center
Dayton, Ohio, United States, 45415
University Pointe
West Chester, Ohio, United States, 45069
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Salem Hospital
Salem, Oregon, United States, 97301
United States, Pennsylvania
Delaware County Memorial Hospital
Drexel Hill, Pennsylvania, United States, 19026
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, United States, 18512
Adams Cancer Center
Gettysburg, Pennsylvania, United States, 17325
Cherry Tree Cancer Center
Hanover, Pennsylvania, United States, 17331
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Upper Delaware Valley Cancer Center
Milford, Pennsylvania, United States, 18337
York Hospital
York, Pennsylvania, United States, 17405
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Saint Francis Hospital
Greenville, South Carolina, United States, 29601
United States, Tennessee
Thompson Cancer Survival Center - West
Knoxville, Tennessee, United States, 37392
Thompson Cancer Survival Center at Methodist
Oak Ridge, Tennessee, United States, 37830
United States, Texas
University of Texas Medical Branch at Galveston
Galveston, Texas, United States, 77555-0565
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Covenant Medical Center-Lakeside
Lubbock, Texas, United States, 79410
United States, Utah
American Fork Hospital
American Fork, Utah, United States, 84003
Sandra L Maxwell Cancer Center
Cedar City, Utah, United States, 84720
Logan Regional Hospital
Logan, Utah, United States, 84321
Cottonwood Hospital Medical Center
Murray, Utah, United States, 84107
Intermountain Medical Center
Murray, Utah, United States, 84157
McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
Utah Valley Regional Medical Center
Provo, Utah, United States, 84604-3337
Dixie Medical Center Regional Cancer Center
Saint George, Utah, United States, 84770
LDS Hospital
Salt Lake City, Utah, United States, 84143
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
Intermountain Health Care
Salt Lake City, Utah, United States, 84103
Utah Cancer Specialists-Salt Lake City
Salt Lake City, Utah, United States, 84106
United States, Vermont
Fletcher Allen Health Care-Medical Center
Burlington, Vermont, United States, 05401
University of Vermont
Burlington, Vermont, United States, 05401
Norris Cotton Cancer Center-North
Saint Johnsbury, Vermont, United States, 05819
United States, West Virginia
Wheeling Hospital
Wheeling, West Virginia, United States, 26003
United States, Wisconsin
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, United States, 54303
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, United States, 54301-3526
Saint Vincent Hospital
Green Bay, Wisconsin, United States, 54301
Saint Mary's Hospital
Green Bay, Wisconsin, United States, 54303
Gundersen Lutheran
La Crosse, Wisconsin, United States, 54601
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Bay Area Medical Center
Marinette, Wisconsin, United States, 54143
Green Bay Oncology - Oconto Falls
Oconto Falls, Wisconsin, United States, 54154
Green Bay Oncology - Sturgeon Bay
Sturgeon Bay, Wisconsin, United States, 54235
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
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 July 23, 2014