MDACC Study Summary 2007-0395

Study Summary
No. 2007-0395:.......Sarcoma......Shreyaskumar R. Patel......Sarcoma Medical Oncology

Study Summary Title



Study Summary Number:	2007-0395

Study Title:	SARC 009: A Phase II Trial of Dasatinib in Advanced Sarcoma

Physician

New Patient Referral



Name:	Shreyaskumar R. Patel	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Sarcoma Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-3626 Contact us about clinical trials

General Information



Disease Group:	Sarcoma	Supported By:	Bristol-Myers Squibb Pharmaceutical Research Institute Sarcoma Alliance for Research through Collaboration, SARC

Phase of Study:	Phase II	Return Visit:	Prestudy visit Every 4 wks for the first 6 mos, then every 6 weeks for the next 6 mos, and then every 3 mos while in the treatment portion of the study. Repeat CT or MRI every 2 mos for 6 mos, then every 3 mos for 2 years from registration.

Treatment Agents:	Dasatinib	Home Care:	Patients will self administer Dasatinib orally twice daily at home.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	None


Description/ Intervention:	The goal of this clinical research study is to learn if dasatinib can help to control the disease in patients with advanced sarcoma. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary objectives

1. To estimate the response rate, defined as objective response at 2, 4 or 6 months or stable disease at 6 months, of dasatinib self-administered daily in subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade (mesenchymal and dedifferentiated) chondrosarcomas, Ewing's sarcoma, pleomorphic undifferentiated sarcoma (MFH), rhabdomyosarcoma, and MPNST.

2. To estimate the 6-month progression-free survival rate of "indolent" sarcomas to include alveolar soft part sarcoma (ASPS), chordoma, epithelioid sarcoma, hemangiopericytoma, giant cell tumor of bone and conventional (Grades 1 and 2) chondrosarcoma treated with dasatinib.

3. To estimate the 6-month progression-free survival rate of gastrointestinal stromal tumors.

Secondary objectives

1. To estimate the 2, 4 and 6 month progression-free survival rates and median time- to-progression of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade (mesenchymal and dedifferentiated) chondrosarcomas, Ewing's sarcoma, MFH, rhabdomyosarcoma, and MPNST treated with dasatinib.

2. To estimate the 2 and 4 month progression-free survival rate and median time-to progression of subjects with "indolent" sarcomas treated with dasatinib.

3. To est. the 2 & 4 month progression-free survival rate & median time-to-progression of subjects with GIST treated with dasatinib.

4. To est. the overall survival rates at 2 & 5 yrs from registration of subjects treated with dasatinib.

5. To collect information about clinically significant adverse events & serious adverse events in subjects with sarcoma treated with dasatinib.

6. To prospectively collect uni-dimensional & bi-dimensional tumor size, tumor volumes & tumor average density determined by computer-aided automated detection in a subset of subjects with tumor predominantly involving the lung.

7. Obtain tumor tissue for creation of tissue microarrays to examine the frequency of kinase expression such as SRC and/or FAK in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, ASPS, chordoma, epithelioid sarcoma, giant cell tumor of bone &
hemangiopericytoma, & GIST if activity of the drug in a subtype warrants further study.

8. Obtain tumor tissue to examine the frequency of mutations in kinases such as PDGFR in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, ASPS, chordoma, epithelioid sarcoma, giant cell tumor of bone & hemangiopericytoma & GIST if activity of the drug in a subtype warrants further study.

9. Obtain blood samples to characterize plasma level of dasatinib & inhibition of SRC and/or FAK in peripheral blood mononuclear cells 2 hrs after ingestion of drug at 2-4 weeks from the start of treatment if activity of the drug in a sarcoma subtype warrants further study. The correlative plasma drug levels & peripheral blood mononuclear cells will be collected at a subset, principally the University of
MI., of the participating sites

Study Status Information



Study Activation / Registration Date:	01/11/2008

IRB Review and Approval Date:	01/11/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	502

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Unresectable, recurrent, or metastatic histologically-confirmed soft tissue or bone sarcoma of one of the following subtypes:Leiomyosarcoma, Liposarcoma, MFH/pleomorphic undifferentiated sarcoma, Rhabdomyosarcoma, Malignant peripheral nerve sheath tumor, 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 tumors (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, CT, 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 as defined by absolute neutrophil count >/= 1,500/ul and platelet count >/= 75,000 within 14 days prior to registration.

7) PT (or INR) and PTT </= 1.5 times the institutional upper limit of normal within 14 days prior to registration.

8) Serum creatinine </= 2.0 times the institutional upper limit of normal within 14 days prior to registration.

9) Serum magnesium, potassium and adjusted (or ionized) calcium >/= the institutional lower limit of normal. (Supplementation of electrolytes prior to screening is allowed).

10) Left ventricular ejection fraction >/= 45% measured by echocardiogram or 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 who 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) Subject weight >/= 50 kg because there is limited experience with dasatinib in subjects weighing less than 50 kg.

15) Subjects must be >/= 13 years of age at the time the consent document is signed by the subject or guardian. 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 micronthick 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.

Links

Registration Number: NCT00464620
Study Information on Clinical Trials Registry (clinicaltrials.gov)