A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas

Exclusion Criteria

• •1. Treatment with investigational agents within the last 4 weeks
• •2. Prior anticancer therapy, within the last 3 weeks of trial dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy
• •3. Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on ECG, marked baseline prolongation of QT/QTc (\[corrected QT interval \]) interval, e.g., repeated demonstration of a QTc interval \> 500 msec; Long QT Syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes.
• •4. Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
• •5. Concurrent second malignancy
• •6. History of hypersensitivity to doxorubicin
• •7. A. For dose escalation phase: More than two prior doses of anthracycline, more than three prior lines of chemotherapy given for metastatic disease B. For MTD expansion phase: Prior chemotherapy
• •8. Bowel obstruction or impending bowel obstruction
• •9. Known HIV positivity
• •10. LVEF (\[left ventricular ejection fraction\]) below normal range (45% by MUGA)
• •11. Presence of metastatic disease that, in the opinion of the investigator, would require palliative treatment within 4 weeks of enrolment