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Trial of Dasatinib in Advanced Sarcomas
This study is currently recruiting participants.
Verified by Sarcoma Alliance for Research through Collaboration, December 2008
Sponsors and Collaborators: Sarcoma Alliance for Research through Collaboration
Bristol-Myers Squibb
Information provided by: Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier: NCT00464620
  Purpose

This study will examine the response rate and the 6-month progression-free survival rates of subjects with advanced sarcoma treated with dasatinib.


Condition Intervention Phase
MFH/Pleomorphic Undifferentiated Sarcoma
Rhabdomyosarcoma
Malignant Peripheral Nerve Sheath Tumors
Osteosarcoma
Chondrosarcoma
Sarcoma, Ewing's
Sarcoma, Alveolar Soft Part
Chordoma
Epithelioid Sarcoma
Giant Cell Tumor of Bone
Hemangiopericytoma
Gastrointestinal Stromal Tumor (GIST)
Drug: Dasatinib
Phase II

MedlinePlus related topics: Bone Cancer Cancer Soft Tissue Sarcoma
Drug Information available for: Dasatinib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Efficacy Study
Official Title: A Phase II Trial of Dasatinib in Advanced Sarcomas

Further study details as provided by Sarcoma Alliance for Research through Collaboration:

Primary Outcome Measures:
  • Evaluation of all lesions for progression or response will be made at 2-month intervals for the first 6 months and then every 3 months thereafter [ Time Frame: every 2 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 502
Study Start Date: May 2007
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Dasatinib
    oral agent, continuous dosing, Cycles = 28 days
Detailed Description:

Further details provided by SARC (Sarcoma Alliance for Research through Collaboration):

Treatment: Subjects take Dasatinib twice daily by mouth for 28 days per 28 day cycle.

Subjects will be seen for interim medical history, physical exam and laboratory studies prior to each cycle. Subjects will undergo tumor imaging every 2 months (8 weeks) for the first 6 months and approximately every 3 months thereafter while on treatment.

A blood sample for collection of specimens with which to later study serum level of Dasatinib and effects on biomarkers of drug activity will be obtained approximately 2 to 4 weeks after the start of treatment.

Central collection of archival tumor with which to later study the frequency of expression and/or mutation of kinases inhibited by dasatinib will occur.

Subjects will be followed for approximately every 3 months until 2 years from registration and then approximately yearly until 5 years from registration.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Unresectable, recurrent, or metastatic histologically-confirmed soft tissue or bone sarcoma of one of the following subtypes:

    • Leiomyosarcoma --* NO LONGER ELIGIBLE*
    • Liposarcoma--* NO LONGER ELIGIBLE*
    • Malignant fibrous histiocytoma (MFH)/pleomorphic undifferentiated sarcoma
    • Rhabdomyosarcoma
    • Malignant peripheral nerve sheath tumor (MPNST)
    • Osteosarcoma (skeletal or extraosseous)
    • Chondrosarcoma
    • Ewing's
    • Alveolar soft part sarcoma
    • Chordoma
    • Epithelioid sarcoma
    • Giant cell tumor of bone
    • Hemangiopericytoma/solitary fibrous tumor
    • Gastrointestinal Stromal Tumor (GIST)
  2. Documentation that subjects with leiomyosarcoma, liposarcoma, osteosarcoma, Ewing's, MPNST, rhabdomyosarcoma or MFH have received, not been eligible for or refused at least one prior chemotherapy regimen before participation in the dasatinib study. Subjects with GIST must have received or been intolerant to imatinib; prior treatment with other agents including sunitinib is not required.Neoadjuvant/adjuvant chemotherapy qualifies as prior therapy.
  3. Subjects must have unidimensionally measurable lesion(s) either by x-ray, computed tomography (CT), magnetic resonance imaging (MRI) or physical examination documented within 30 days prior to registration.
  4. Prior radiation will be allowed. More than two weeks should have elapsed since the administration of the last fraction of radiation therapy, and subjects must have recovered from grade 2 or higher associated toxicities. Measurable lesions, which are selected as target lesions, must be outside previously radiated fields or have documented progression no sooner than 6 weeks after completion of radiation.
  5. More than 2 weeks must have elapsed since the subject has received any prior systemic chemotherapy (6 weeks for mitomycin C), and the patient should have recovered from toxicities to the baseline prior to the last course of chemotherapy.
  6. Adequate hematologic function within 14 days prior to registration.
  7. PT (or INR) and PTT ≤ 1.5 times the institutional ULN within 14 days prior to registration.
  8. Serum creatinine ≤ 2.0 times the institutional ULN within 14 days prior to registration.
  9. Serum magnesium, potassium and adjusted (or ionized) calcium ≥ the institutional LLN. (Supplementation of electrolytes prior to screening is allowed).
  10. Left ventricular ejection fraction ≥ 45% measured by echocardiogram or multiple gated acquisition (MUGA) within 30 days prior to registration (but must be performed after the last dose of an anthracycline) for subjects who have received an anthracycline (e.g. doxorubicin, epirubicin) or have a medical history of cardiac disease. The measurement of left ventricular ejection fraction is not required of subjects whom have not received cardiotoxic chemotherapy (e.g. anthracycline) and do not have a medical history of cardiac disease.
  11. Sexually active women and men of childbearing potential must agree to use an effective method of birth control during the course of the study and for up to 3 months following the last dose of the study drug, in a manner such that risk of pregnancy is minimized. Surgical sterilization, intrauterine device or barrier method (e.g. condom and/or diaphragm with spermicidal agents) are acceptable forms of birth control.
  12. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to treatment. A pregnancy test is not required for registration. Women who have not menstruated for more than 2 years will be considered postmenopausal, thus not of childbearing potential.
  13. ECOG performance score 0, 1 or 2.
  14. Weight ≥ 50 kg because there is limited experience with dasatinib in subjects weighing less than 50 kg.
  15. ≥13 years of age Minors will be required to sign an assent document prior to treatment.
  16. Subjects must be able to swallow whole tablets.
  17. Subjects must be informed of the investigational nature of the study and provide written, informed consent and authorization to release protected health information using a document(s) approved by the investigator's institution.
  18. A paraffin block, either from a previous surgery or recent biopsy, should be available for correlative studies. If a block of tumor is not available, at least 8 unstained slides of tumor sample, 1 H&E and three (3) 15 micron-thick sections in an eppendorf tube for DNA extraction from a representative portion of the sarcoma may be substituted after discussion with and approval from the study Principal Investigator.

Exclusion Criteria:

  1. Subjects who are curable by conventional multidisciplinary management.
  2. Subjects with symptomatic central nervous system metastasis.
  3. Women who are pregnant or nursing/breastfeeding.
  4. History of significant bleeding disorder unrelated to cancer, including:

    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
    • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  5. Subjects currently taking medications that inhibit platelet function (i.e., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, and any non-steroidal anti-inflammatory drug) because of a potential increased risk of bleeding from dasatinib.
  6. Subjects currently taking anticoagulants (warfarin, heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]) because of a potential increased risk of bleeding from dasatinib.
  7. Diagnosis of unstable angina or myocardial infarction within 6 months of study entry.
  8. Subjects currently taking one or more of the following drugs that are generally accepted to have a risk of causing Torsades de Pointes:

    • Quinidine, procainamide, disopyramide
    • Amiodarone, sotalol, ibutilide, dofetilide
    • Erythromycins, clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
  9. Diagnosed or suspected congenital long QT syndrome.
  10. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) within 30 days prior to study registration.
  11. Subjects unable or unwilling to suspend treatment with bisphosphonates for at least the first 8 weeks of treatment with study drug because of the risk of hypocalcemia caused by dasatinib.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00464620

Contacts
Contact: Denise Reinke, MS, NP, President 734-930-7600 sarc@sarctrials.org
Contact: Kathleen Granlund 734-930-7607 kegranlund@sarctrials.org

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Bryce Warren         WarrenBryceA@uams.edu    
Principal Investigator: Kimo Stine            
United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Maria Ahern     650-725-6413     mahern@stanford.edu    
Principal Investigator: Kristen Ganjoo, MD            
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Neeti Arora     626-256-4673 ext 63019     NArora@coh.org    
Principal Investigator: Warren Chow, MD            
Sarcoma Oncology Center Recruiting
Santa Monica, California, United States, 90403
Contact: Viky Chua     310-552-9999     vikychua@aol.com    
Principal Investigator: Sant Chawla            
Cedars-Sinai Outpatient Cancer Center Recruiting
Los Angeles, California, United States, 90048
Contact: Chi Vu     310-423-2133     CVu@csocc.com    
Principal Investigator: Charles Forscher, MD            
United States, District of Columbia
Washington Cancer Institute Recruiting
Washington, District of Columbia, United States, 20010
Contact: Christina Sheeran     202-877-5371     Christina.M.Sheeran@medstar.net    
Principal Investigator: Dennis A Priebat, MD            
United States, Georgia
Winship Cancer Institute at Emory University Recruiting
Atlanta, Georgia, United States, 30308
Contact: Ernest Evans     404-686-1855     ernest.evans@emoryhealthcare.org    
Principal Investigator: Gina D'Amato, MD            
United States, Idaho
Kootenai Cancer Center Recruiting
Coeur d'Alene, Idaho, United States, 83814
Contact: Sheryl Golden     208-666-2093     sgolden@kmc.org    
Principal Investigator: Brian Samuels, MD            
United States, Illinois
Oncology Specialists Recruiting
Park Ridge, Illinois, United States, 60068
Contact: Kathy Tolzien     847-268-8569     ktolzien@oncmed.net    
Principal Investigator: Pamela Kaiser, MD            
United States, Indiana
Indiana University Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kristen Potter, MS     317-278-6616     krpotter@iupui.edu    
Principal Investigator: Daniel Rushing, MD            
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Melanie Frees, RN, BSN, CCRC     319-356-1228     melanie-frees@uiowa.edu    
Principal Investigator: Mohammed Milhem, MD            
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Adult Oncology     410-955-8804        
Contact: Pediatric Oncology     410-955-8751        
Principal Investigator: David Loeb, MD, PhD            
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Anthony Thomas     617-643-5411     athomas2@partners.org    
Principal Investigator: Edwin Choy, MD            
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Sarah Solomon     617-582-7503     ssolomon1@partners.org    
Principal Investigator: James Butrynski, MD            
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Gino Metko     734-647-2095     ginom@med.umich.edu    
Principal Investigator: Scott Schuetze, MD, PhD            
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Gladys Pierce     402-354-5129     Gladys.Pierce@nmhs.org    
Principal Investigator: Kirsten Leu, MD            
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates Recruiting
Philadelphia, Pennsylvania, United States, 19106
Contact: Deb Riordan, RN, BS     215-829-6712     debbieriordan@pennoncology.com    
Principal Investigator: Arthur Staddon, MD            
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Monica Davey     215-728-5534     M_Davey@fccc.edu    
Principal Investigator: Margaret von Mehren, MD            
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Lynne Frydrych     412-623-4036     frydrychlm2@upmc.edu    
Principal Investigator: Hussein Tawbi, MD, MSc            
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Joanne Gigstad     713-563-0510     jgigstad@mdanderson.org    
Principal Investigator: Shreyas Patel, MD            
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Bristol-Myers Squibb
Investigators
Principal Investigator: Scott Schuetze, MD, PhD University of Michigan
  More Information

SARC Website  This link exits the ClinicalTrials.gov site

Responsible Party: SARC ( Denise Reinke, MS, NP, President )
Study ID Numbers: SARC009
Study First Received: April 20, 2007
Last Updated: December 17, 2008
ClinicalTrials.gov Identifier: NCT00464620  
Health Authority: United States: Institutional Review Board

Keywords provided by Sarcoma Alliance for Research through Collaboration:
Dasatinib
MFH/pleomorphic undifferentiated sarcoma
Rhabdomyosarcoma
Malignant peripheral nerve sheath tumor
Osteosarcoma (skeletal or extra osseous)
Chondrosarcoma
Ewing's
Alveolar soft part sarcoma (ASPS)
Chordoma
Epithelioid sarcoma
Giant cell tumor of bone
Hemangiopericytoma/solitary fibrous tumor
Gastrointestinal Stromal Tumor (GIST)

Study placed in the following topic categories:
Bone Neoplasms
Gastrointestinal Diseases
Epithelioid sarcoma
Malignant mesenchymal tumor
Bone neoplasms
Alveolar soft part sarcoma
Giant Cell Tumor of Bone
Osteogenic sarcoma
Chordoma
Bone Diseases
Soft tissue sarcomas
Neoplasms, Connective and Soft Tissue
Ewing's sarcoma
Giant Cell Tumors
Sarcoma, Ewing's
Nerve sheath neoplasm
Musculoskeletal Diseases
Neuromuscular Diseases
Dasatinib
Neoplasms, Germ Cell and Embryonal
Chondrosarcoma
Sarcoma, Alveolar Soft Part
Embryonal sarcoma
Nervous System Neoplasms
Rhabdomyosarcoma
Digestive System Neoplasms
Osteosarcoma
Hemangiopericytoma
Digestive System Diseases
Peripheral Nervous System Diseases

Additional relevant MeSH terms:
Neoplasms, Muscle Tissue
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Myosarcoma
Neoplasms, Nerve Tissue
Nervous System Diseases
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Neoplasms, Bone Tissue
Neoplasms, Vascular Tissue
Neoplasms, Connective Tissue

ClinicalTrials.gov processed this record on January 16, 2009