Trial of Dasatinib in Advanced Sarcomas

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier:
NCT00464620
First received: April 20, 2007
Last updated: June 17, 2014
Last verified: June 2014
  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
Rhabdomyosarcoma
Malignant Peripheral Nerve Sheath Tumors
Chondrosarcoma
Sarcoma, Ewing's
Sarcoma, Alveolar Soft Part
Chordoma
Epithelioid Sarcoma
Giant Cell Tumor of Bone
Hemangiopericytoma
Gastrointestinal Stromal Tumor (GIST)
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Dasatinib in Advanced Sarcomas

Resource links provided by NLM:


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 Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (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--* NO LONGER ELIGIBLE*
    • Rhabdomyosarcoma --* NO LONGER ELIGIBLE*
    • Malignant peripheral nerve sheath tumor (MPNST) --* NO LONGER ELIGIBLE*
    • Osteosarcoma (skeletal or extraosseous)--* NO LONGER ELIGIBLE*
    • Ewing's --* NO LONGER ELIGIBLE*
    • Chondrosarcoma
    • Alveolar soft part sarcoma
    • Chordoma
    • Epithelioid sarcoma
    • Giant cell tumor of bone
    • Hemangiopericytoma/solitary fibrous tumor
    • Gastrointestinal Stromal Tumor (GIST) --* NO LONGER ELIGIBLE*
  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
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: NCT00464620

Locations
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
City of Hope
Duarte, California, United States, 91010
Cedars-Sinai Outpatient Cancer Center
Los Angeles, California, United States, 90048
Stanford University
Palo Alto, California, United States, 94304
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
United States, District of Columbia
Washington Cancer Institute
Washington, District of Columbia, United States, 20010
United States, Georgia
Winship Cancer Institute at Emory University
Atlanta, Georgia, United States, 30308
United States, Idaho
Kootenai Cancer Center
Coeur d'Alene, Idaho, United States, 83814
United States, Illinois
Oncology Specialists
Park Ridge, Illinois, United States, 60068
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
MD Anderson
Houston, Texas, United States, 77030
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Bristol-Myers Squibb
Investigators
Principal Investigator: Scott Schuetze, MD, PhD University of Michigan
  More Information

Additional Information:
No publications provided

Responsible Party: Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier: NCT00464620     History of Changes
Other Study ID Numbers: SARC009
Study First Received: April 20, 2007
Last Updated: June 17, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Sarcoma
Gastrointestinal Stromal Tumors
Rhabdomyosarcoma
Chondrosarcoma
Chordoma
Hemangiopericytoma
Neoplasms
Nerve Sheath Neoplasms
Giant Cell Tumors
Neurofibrosarcoma
Neurilemmoma
Bone Neoplasms
Giant Cell Tumor of Bone
Sarcoma, Ewing
Sarcoma, Alveolar Soft Part
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Vascular Tissue
Neoplasms, Nerve Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases

ClinicalTrials.gov processed this record on September 16, 2014