Study of PXD101 and Doxorubicin to Treat Soft Tissue Sarcomas

The present PXD101-CLN-14 study is an open-label non-randomized, multicenter, phase I/II trial to assess the efficacy and safety of PXD101 in combination with doxorubicin in patients with soft tissue sarcomas (and in the dose escalation phase all solid tumours) in need of chemotherapy.

This trial is an open-label, multicentre, dose-escalation Phase I/II study to evaluate safety, efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with doxorubicin administered q 3 weeks in patients with advanced solid tumours. Once the MTD has been established, up to a total of 20-40 patients with STS may be enrolled at the MTD dose level to examine efficacy and safety in this specific patient population. The trial is stopped if no more than 2 responses are seen among the first 20 of these patients.

Inclusion Criteria: (abbreviated)

1. Signed consent
2. For the dose escalation phase: patients with histological or cytological confirmed solid tumours.
3. For the MTD expansion phase: patients with an established diagnosis of soft tissue sarcoma in need of first line chemotherapy and with measurable disease
4. Performance status (ECOG) ≤ 2
5. Life expectancy of at least 3 months
6. Age ≥ 18 years
7. Acceptable liver, renal and bone marrow function as defined
8. Acceptable coagulation status as defined

Exclusion Criteria:

1. Treatment with investigational agents within the last 4 weeks
2. Prior anticancer therapy, within the last 3 weeks of trial
3. Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease
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 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