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: January 5, 2016
Last verified: November 2015
  Purpose
This phase II trial studies how well dasatinib works in treating patients with glioblastoma multiforme or gliosarcoma that has come back. 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 Neoplasm
Drug: Dasatinib
Other: Pharmacological Study
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:
  • Number of Patients Achieving 6-month Progression-free Survival (6mPFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    This study utilized a two-stage phase II design (Stage 1B and 2). The primary endpoint of 6-month progression-free survival (6mPFS) would be assessed based on the patients combined from 1B and 2 if the study continued to Stage 2. Null hypothesis = 11%; alternative hypothesis = 25%. Simon's minmax 2-stage design was used with type I and type II error both set at 10%. If the first stage met its criteria (see secondary outcome measure), then accrual would continue, otherwise there would be no further accrual and the alternative hypothesis would be rejected. Following Stage 2 accrual completion and 6 months of follow-up, if 9 or more patients were alive without progression by 6 months, the null hypothesis would be rejected in favor of the alternative.


Secondary Outcome Measures:
  • Number of Patients Achieving Objective Response (Partial or Complete Response) OR 6-month Progression-free Survival (6mPFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Study design and efficacy determination uses the hybrid endpoint of 6mPFS or complete/partial response of any duration prior to or at 6 months. Null hypothesis = 11%; alternative hypothesis = 25%. Simon's minmax 2-stage design was used with type I and type II error both set at 10%. Stage 1 and 1B: If 2 or fewer patients were alive and progression-free at 6 months or achieved complete/partial response, then there would be no further accrual and the alternative hypothesis would be rejected. Otherwise accrual would continue to a total of 50 analyzable patients to address the primary endpoint.

  • 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 [Complete Response (CR), Partial Response (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.


Enrollment: 64
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 dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: Pharmacological Study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the therapeutic efficacy of dasatinib in all patients (i.e., stages 1B and 2 combined) with recurrent/progressive glioblastoma (GBM) as measured by 6-month progression-free survival.

SECONDARY OBJECTIVES:

I. To determine the therapeutic efficacy of dasatinib for stage 1B patients with recurrent/progressive GBM as measured by a hybrid endpoint of 6-month progression-free survival OR objective response of (complete response [CR] or partial response [PR]) rate.

II. To determine patient overall survival. III. To determine the toxicity of dasatinib in the treatment of patients with GBM.

IV. To determine radiographic response rate to treatment. V. To determine patient progression-free survival. VI. To explore molecular correlates of clinical outcome. VII. To explore pharmacokinetic correlates of dosing, toxicity, and efficacy.

OUTLINE:

Patients receive dasatinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.

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

  Eligibility

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

Inclusion Criteria:

  • Histologically proven diagnosis of GBM; gliosarcoma is also an eligible diagnosis
  • The patient must consent to submission of tissue for central pathology review
  • Patients who have already undergone central pathology review through their enrollment on another Radiation Therapy Oncology Group (RTOG) GBM trial do not need to consent to having their material re-reviewed by the central pathologist for this study
  • All patients must consent to molecular analysis of pre-dasatinib tumor tissue
  • Patients accrued to stage I (closed to accrual) or stage IB (opened to accrual May 5, 2009) must have tumors overexpressing at least 2 known dasatinib targets (i.e., SRC proto-oncogene, non-receptor tyrosine kinase [SRC], v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [KIT], platelet-derived growth factor receptor [PDGFR], or ephrin type-A receptor 2 [EPHA2])
  • Patients accrued to stage II (cohort closed; not currently applicable) do not require overexpression of SRC, KIT, PDGFR, or EPHA2
  • History and physical examination, including height and weight, within 10 days prior to registration on study
  • Brain magnetic resonance imaging (MRI) with and without gadolinium within 10 days prior to registration on study
  • Contrast-enhanced computed tomography (CT) scans are allowed for patients who cannot undergo MRI scanning
  • Karnofsky performance status >= 60
  • Absolute neutrophil count (ANC) >= 1,000 cells/mm^3
  • Platelets >= 75,000 cells/mm^3
  • Hemoglobin (Hgb) >= 8.0 g/dl; (note: the use of transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable)
  • Leukocytes >= 3,000 cells/mm^3
  • Absolute lymphocyte count (ALC) >= 500 cells/mm^3
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional upper limit of normal
  • Creatinine =< 3 X institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • All patients must have undergone prior treatment with radiotherapy and temozolomide; no other prior treatments are allowed
  • There must be unequivocal radiographic evidence for tumor progression by MRI or CT scan, and the same type of scan (i.e., MRI or CT) must be used throughout the period of protocol treatment for tumor measurement; patients must be on a stable or decreasing dose of corticosteroids for at least 5 days before the baseline MRI/CT is performed
  • Patients having undergone recent surgery for recurrent/progressive disease are eligible as long as they have recovered from the effects of surgery; patients who recently underwent resection without measurable disease post-operatively are also eligible
  • Measurable disease is not required for eligibility in patients who recently underwent resection as long as the following conditions are met as applicable:

    • Progression of disease led to the surgery
    • 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
  • Women of childbearing potential must have a negative beta human chorionic gonadotropin (B HCG) pregnancy test =< 3 days prior to registration
  • Patient must sign study-specific informed consent prior to study entry

Exclusion Criteria:

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Radiotherapy within 4 weeks or temozolomide within 14 days prior to registration or failure to recover from adverse events of either radiotherapy or temozolomide
  • Patients may not be receiving any other investigational agents
  • Severe, active comorbidity, defined as follows:

    • Any clinically significant cardiovascular disease including 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 corrected QT interval (QTc) > 480 msec (Fridericia correction)
      • Ejection fraction less than institutional normal
      • Major conduction abnormality (unless a cardiac pacemaker is present)
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; breastfeeding should be discontinued if the mother is treated with dasatinib
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib
  • Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible
  • Patients must not be taking hepatic enzyme inducing antiepileptic drugs (EIAEDs); if patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for >= 2 weeks prior to initiation of dasatinib
  • Patients who require antacids should use short-acting, locally active agents (e.g., Maalox, Mylanta etc.); however, these agents should not be taken within either 2 hours before or 2 hours after the dasatinib dose
  • Use of antithrombotic and/or antiplatelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, clopidogrel, ticlopidine, Aggrenox)
  • Use of ibuprofen or non-steroidal anti-inflammatory drugs (NSAIDs)
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded
  • Prior treatment with stereotactic radiosurgery (including Gamma-Knife, Cyberknife, or other variants) or brachytherapy
  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
The University of Arizona Medical Center-University Campus
Tucson, Arizona, United States, 85724
United States, California
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, United States, 95603
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, United States, 95682
Mercy San Juan Medical Center
Carmichael, California, United States, 95608
Glendale Adventist Medical Center
Glendale, California, United States, 91206
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, United States, 95661
Mercy General Hospital Radiation Oncology Center
Sacramento, California, United States, 95819
Radiological Associates of Sacramento
Sacramento, California, United States, 95815
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Vacaville, California, United States, 95687
United States, Connecticut
Smilow Cancer Hospital Care Center at Saint Francis
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 University Medical Center
Savannah, Georgia, United States, 31404
United States, Indiana
IU Health Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Kansas
Saint Luke's South Hospital
Overland Park, Kansas, United States, 66213
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Kansas City NCI Community Oncology Research Program
Prairie Village, Kansas, United States, 66208
Shawnee Mission Medical Center-KCCC
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 CCOP
Ann Arbor, Michigan, United States, 48106
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
Oakwood Hospital and Medical Center
Dearborn, Michigan, United States, 48124
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Green Bay Oncology - Escanaba
Escanaba, Michigan, United States, 49829
Hurley Medical Center
Flint, Michigan, United States, 48502
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States, 48532
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
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
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States, 55109
Minnesota Oncology Hematology PA-Maplewood
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
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States, 55416
Park Nicollet Clinic - Saint Louis Park
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
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States, 64111
Saint Joseph Health Center
Kansas City, Missouri, United States, 64114
Truman Medical Center
Kansas City, Missouri, United States, 64108
Heartland Hematology and Oncology Associates Incorporated
Kansas City, Missouri, United States, 64118
Research Medical Center
Kansas City, Missouri, United States, 64132
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, United States, 64086
Liberty Radiation Oncology Center
Liberty, Missouri, United States, 64068
Liberty Hospital
Liberty, Missouri, United States, 64068
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
Cancer Research for the Ozarks NCORP
Springfield, Missouri, United States, 65804
CoxHealth South Hospital
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
Virtua Memorial
Mount Holly, New Jersey, United States, 08060
Sparta Cancer Treatment Center
Sparta, New Jersey, United States, 07871
Virtua 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
WellSpan Health-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, 37932
Thompson Cancer Survival Center at Methodist
Oak Ridge, Tennessee, United States, 37830
United States, Texas
University of Texas Medical Branch
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
Dixie Medical Center Regional Cancer Center
Saint George, Utah, United States, 84770
Intermountain Health Care
Salt Lake City, Utah, United States, 84103
Utah Cancer Specialists-Salt Lake City
Salt Lake City, Utah, United States, 84106
LDS Hospital
Salt Lake City, Utah, United States, 84143
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
United States, Vermont
University of Vermont College of Medicine
Burlington, Vermont, United States, 05405
University of Vermont Medical Center
Burlington, Vermont, United States, 05401
Norris Cotton Cancer Center-North
Saint Johnsbury, Vermont, United States, 05819
United States, West Virginia
Wheeling Hospital/Schiffler Cancer Center
Wheeling, West Virginia, United States, 26003
United States, Wisconsin
Saint Mary's Hospital
Green Bay, Wisconsin, United States, 54303
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, United States, 54301-3526
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, United States, 54303
Saint Vincent Hospital
Green Bay, Wisconsin, United States, 54301
Gundersen Lutheran Medical Center
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, Quebec
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
Quebec City, Quebec, Canada, G1R 2J6
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Saudi Arabia
King Faisal Specialist Hospital and Research Centre
Riyadh, Saudi Arabia, 11211
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Andrew Lassman NRG Oncology
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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  U10CA180868  U10CA021661 
Study First Received: January 16, 2007
Results First Received: June 19, 2014
Last Updated: January 5, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on February 09, 2016