Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

NCT ID: NCT00423735

Last Updated: 2019-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-24
• Study Completion Date: 2018-09-04

Brief Summary

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.

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.

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Given PO

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

Dasatinib

Given PO

Intervention Type: DRUG

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BMS-354825; Sprycel

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Lassman

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Mobile Infirmary Medical Center

Mobile, Alabama, United States

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States

The University of Arizona Medical Center-University Campus

Tucson, Arizona, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, United States

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Cameron Park, California, United States

Mercy San Juan Medical Center

Carmichael, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Glendale Adventist Medical Center

Glendale, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Mercy General Hospital Radiation Oncology Center

Sacramento, California, United States

Sutter Cancer Centers Radiation Oncology Services-Vacaville

Vacaville, California, United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Boca Raton Regional Hospital

Boca Raton, Florida, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Integrated Community Oncology Network-Southside Cancer Center

Jacksonville, Florida, United States

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, United States

Baptist Medical Center South

Jacksonville, Florida, United States

Integrated Community Oncology Network-Florida Cancer Center Beaches

Jacksonville Beach, Florida, United States

Jupiter Medical Center

Jupiter, Florida, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

21st Century Oncology-Orange Park

Orange Park, Florida, United States

21st Century Oncology-Palatka

Palatka, Florida, United States

Bay Medical Center

Panama City, Florida, United States

Integrated Community Oncology Network-Flager Cancer Center

Saint Augustine, Florida, United States

John B Amos Cancer Center

Columbus, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Saint John's Hospital

Springfield, Illinois, United States

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, United States

Franciscan Saint Francis Health-Beech Grove

Beech Grove, Indiana, United States

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Reid Health

Richmond, Indiana, United States

Menorah Medical Center

Overland Park, Kansas, United States

Saint Luke's South Hospital

Overland Park, Kansas, United States

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, United States

Shawnee Mission Medical Center-KCCC

Shawnee Mission, Kansas, United States

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Boston Medical Center

Boston, Massachusetts, United States

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Beaumont Hospital-Dearborn

Dearborn, Michigan, United States

Ascension Saint John Hospital

Detroit, Michigan, United States

Green Bay Oncology - Escanaba

Escanaba, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Green Bay Oncology - Iron Mountain

Iron Mountain, Michigan, United States

Allegiance Health

Jackson, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

Sparrow Hospital

Lansing, Michigan, United States

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Lake Huron Medical Center

Port Huron, Michigan, United States

Saint Mary's of Michigan

Saginaw, Michigan, United States

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Mercy Hospital

Coon Rapids, Minnesota, United States

Fairview-Southdale Hospital

Edina, Minnesota, United States

Unity Hospital

Fridley, Minnesota, United States

Hutchinson Area Health Care

Hutchinson, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, United States

Saint John's Hospital - Healtheast

Maplewood, Minnesota, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

North Memorial Medical Health Center

Robbinsdale, Minnesota, United States

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Regions Hospital

Saint Paul, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

Saint Francis Regional Medical Center

Shakopee, Minnesota, United States

Ridgeview Medical Center

Waconia, Minnesota, United States

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota, United States

Singing River Hospital

Pascagoula, Mississippi, United States

Cape Radiation Oncology

Cape Girardeau, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Centerpoint Medical Center LLC

Independence, Missouri, United States

Truman Medical Center

Kansas City, Missouri, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Saint Joseph Health Center

Kansas City, Missouri, United States

North Kansas City Hospital

Kansas City, Missouri, United States

Heartland Hematology and Oncology Associates Incorporated

Kansas City, Missouri, United States

Research Medical Center

Kansas City, Missouri, United States

Saint Luke's East - Lee's Summit

Lee's Summit, Missouri, United States

Liberty Radiation Oncology Center

Liberty, Missouri, United States

Heartland Regional Medical Center

Saint Joseph, Missouri, United States

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Renown Regional Medical Center

Reno, Nevada, United States

Cheshire Medical Center-Dartmouth-Hitchcock Keene

Keene, New Hampshire, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Virtua Memorial

Mount Holly, New Jersey, United States

Sparta Cancer Treatment Center

Sparta, New Jersey, United States

Virtua Voorhees

Voorhees Township, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Highland Hospital

Rochester, New York, United States

University of Rochester

Rochester, New York, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Rutherford Hospital

Rutherfordton, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Cleveland Clinic Akron General

Akron, Ohio, United States

Summa Barberton Hospital

Barberton, Ohio, United States

Aultman Health Foundation

Canton, Ohio, United States

University of Cincinnati/Barrett Cancer Center

Cincinnati, Ohio, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital - Dayton

Dayton, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Health Center

Dayton, Ohio, United States

Veteran Affairs Medical Center

Dayton, Ohio, United States

Blanchard Valley Hospital

Findlay, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, United States

Kettering Medical Center

Kettering, Ohio, United States

UH Seidman Cancer Center at Salem Regional Medical Center

Salem, Ohio, United States

Upper Valley Medical Center

Troy, Ohio, United States

University Pointe

West Chester, Ohio, United States

Cancer Treatment Center

Wooster, Ohio, United States

Greene Memorial Hospital

Xenia, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Salem Hospital

Salem, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, United States

Northeast Radiation Oncology Center

Dunmore, Pennsylvania, United States

Adams Cancer Center

Gettysburg, Pennsylvania, United States

Cherry Tree Cancer Center

Hanover, Pennsylvania, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Upper Delaware Valley Cancer Center

Milford, Pennsylvania, United States

Reading Hospital

West Reading, Pennsylvania, United States

WellSpan Health-York Hospital

York, Pennsylvania, United States

AnMed Health Hospital

Anderson, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Saint Francis Hospital

Greenville, South Carolina, United States

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Wellmont Holston Valley Hospital and Medical Center

Kingsport, Tennessee, United States

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Thompson Cancer Survival Center - West

Knoxville, Tennessee, United States

Thompson Cancer Survival Center at Methodist

Oak Ridge, Tennessee, United States

University of Texas Medical Branch

Galveston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Covenant Medical Center-Lakeside

Lubbock, Texas, United States

American Fork Hospital / Huntsman Intermountain Cancer Center

American Fork, Utah, United States

Sandra L Maxwell Cancer Center

Cedar City, Utah, United States

Logan Regional Hospital

Logan, Utah, United States

Cottonwood Hospital Medical Center

Murray, Utah, United States

Intermountain Medical Center

Murray, Utah, United States

McKay-Dee Hospital Center

Ogden, Utah, United States

Utah Valley Regional Medical Center

Provo, Utah, United States

Intermountain Health Care

Salt Lake City, Utah, United States

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Dixie Medical Center Regional Cancer Center

St. George, Utah, United States

University of Vermont Medical Center

Burlington, Vermont, United States

University of Vermont College of Medicine

Burlington, Vermont, United States

Norris Cotton Cancer Center-North

Saint Johnsbury, Vermont, United States

Southwest VA Regional Cancer Center

Norton, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, United States

Green Bay Oncology at Saint Vincent Hospital

Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Bay Area Medical Center

Marinette, Wisconsin, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, United States

Green Bay Oncology - Oconto Falls

Oconto Falls, Wisconsin, United States

Green Bay Oncology - Sturgeon Bay

Sturgeon Bay, Wisconsin, United States

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin, United States

London Regional Cancer Program

London, Ontario, Canada

CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)

Québec, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

King Faisal Specialist Hospital and Research Centre

Riyadh, , Saudi Arabia

Countries

United States; Canada; Saudi Arabia

References

Lassman AB, Pugh SL, Gilbert MR, Aldape KD, Geinoz S, Beumer JH, Christner SM, Komaki R, DeAngelis LM, Gaur R, Youssef E, Wagner H, Won M, Mehta MP. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). Neuro Oncol. 2015 Jul;17(7):992-8. doi: 10.1093/neuonc/nov011. Epub 2015 Mar 10.

Reference Type: DERIVED

PMID: 25758746 (View on PubMed)

Other Identifiers

NCI-2009-00744

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000526070

Identifier Type: -

Identifier Source: secondary_id

RTOG 0627

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0627

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00744

Identifier Type: -

Identifier Source: org_study_id