Trial of Dasatinib in Advanced Sarcomas
Condition: 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)
MeSH terms: Neoplasms; Sarcoma; Gastrointestinal Stromal Tumors; Rhabdomyosarcoma; Chondrosarcoma; Chordoma; Giant Cell Tumors; Nerve Sheath Neoplasms; Neurofibrosarcoma; Hemangiopericytoma; Solitary Fibrous Tumors; Bone Neoplasms; Giant Cell Tumor of Bone; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma, Alveolar Soft Part
Intervention: Dasatinib
Intervention description: oral agent, continuous dosing, Cycles = 28 days
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 366.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No
Keywords: 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)

Summary:

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

Eligibility 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. Prothrombin Time (PT) (or INR) and Partial Thromboplastin Time (PTT) ≤ 1.5 times the
             institutional upper limit of normal (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 lower
             limit of normal (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. Eastern Cooperative Oncology Group (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 corrected QT (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.