A Phase II Study of Oral ENMD-2076 Administered to Patients With Advanced/Metastatic Soft Tissue Sarcoma
- Have documented histological diagnosis of soft tissue sarcoma (e.g. leiomyosarcoma,
synovial sarcoma, angiosarcoma and liposarcoma etc), with the exception of
gastrointestinal stromal tumor (GIST).
- Meet revised RECIST criteria (version 1.1) within 4 weeks of entry by having
measurable disease defined as one or more lesions that can be accurately measured in
one or more dimensions. Areas of previous radiation may not serve as measurable
disease unless there has been objective interval tumor growth documented
- Must have had no more than 1 line of treatment in the advanced/metastatic setting.
The use of prior anti-angiogenic therapy is allowed. Previous neo-adjuvant or
adjuvant therapies are allowed.
- Are at least 3 weeks from major surgery or radiation therapy and recovered; 3 weeks
from any other previous anticancer therapy and recovered including biologics.
- Are ≥ 18 years of age
- The patient has a multigated acquisition (MUGA) scan with an actual left ventricular
ejection fraction of greater than or equal to the institution lower limit of normal
within one month prior to start of study.
- Have clinically acceptable laboratory screening results within certain limits
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) or less than or equal to 5
times ULN if liver metastases are present
- Total bilirubin ≤ 1.5 x ULN
- Creatinine ≤ 1.5 x ULN or > 50 ml/min calculated by the Cockroft and Gault
formula (formula defined in appendix E).
- Absolute neutrophil count ≥ 1500 cells/mm3
- Platelets ≥ 100,000/mm3
- Hemoglobin ≥ 9.0 g/dL
- INR ≤ 1.5
- Have an ECOG performance status of 0 or 1.
- Patients must have and consent for access to archival material (for correlative
studies). Patients who do not have archival material will be eligible if they consent
for fresh tissue biopsy.
- Women of child producing potential must agree to use effective contraceptive methods
prior to study entry, during study participation, and for at least 30 days after the
last administration of study medication. A serum pregnancy test within 72 hours
prior to the initiation of therapy will be required for women of childbearing
- Have the ability to understand the requirements of the study, provide written
informed consent which includes authorization for release of protected health
information, abide by the study restrictions, and agree to return for the required
- Able to tolerate oral medications.
- Women who are pregnant or nursing
- Have active, acute, or chronic clinically significant infections or bleeding.
- Have uncontrolled hypertension (systolic blood pressure greater than 150mmHg or
diastolic blood pressure greater than 100mmHg); or history of congestive heart
failure (equal to or greater than Grade 2 classification by New York Heath
- Have active angina pectoris, stroke or recent myocardial infarction (within 6
- Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater
than 480 msec.
- Have additional uncontrolled serious medical or psychiatric illness.
- Require therapeutic doses of anti-coagulation either by virtue of low-molecular
weight heparin or coumadin (prophylactic anti-coagulation allowed). Patients with
previous history of deep venous thrombosis or pulmonary embolism are also excluded.
- Known CNS metastases
- Have any medical condition that would impair the administration of oral agents
including recurrent bowel obstructions, inflammatory bowel disease or uncontrolled
nausea, vomiting or diarrhea
- Have 2+ protein by urinalysis. Patients with an ongoing or previous history of
nephrotic syndrome will be excluded
- Have an additional malignancy diagnosed within 5 years of study enrollment with the
exception of basal or squamous cell skin cancer or cervical cancer in situ
- Require treatment with drugs known to be potent inducers or inhibitors of CYP3A4 that
cannot be substituted
- Patients who cannot or refuse to stop herbal medications of illicit drug use will be
excluded from the study. Use of medical marijuana is not permissible in this study.