A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas

Inclusion Criteria

• •Participants must have pathologically confirmed soft-tissue sarcoma, which is metastatic or unresectable, sarcoma with no curative multimodality options
• •Participants must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• •No more than two prior lines of chemotherapy for metastatic sarcoma are allowed; Neo-adjuvant/adjuvant chemotherapy with definitive therapy (radiation, surgery or radiation and surgery) will not be counted as one of these prior lines of therapy.
• •Age ≥ 18 and ≤ 75 years.
• •Eastern Cooperative Oncology Group performance status ≤1 (see Appendix A)
• •Life expectancy of greater than 3 months
• •Participants must have normal organ and marrow function as defined below:
• •* Hemoglobin ≥ 9 g/dl
• •* absolute neutrophil count ≥ 1,500/mcL
• •* platelets ≥ 100,000/mcL
• •* total bilirubin ≤ 1.5 X ULN
• •* AST(SGOT)/ALT(SGPT) ≤3 X ULN (including patients with liver metastases)
• •* creatinine ≤1.5 X ULN
• •* CPK \< 2.5 X ULN
• •* Albumin ≥ 3 g/dl
• •Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to receiving study agents.
• •For patients in stratum A, an echocardiogram or multiple gated acquisition scan (MUGA) demonstrating left ventricular ejection fraction \> 50% is required within 30 days prior to study drug administration.
• •Participants must be willing and able to comply with the study scheduled visits, laboratory tests, and other procedures outlined in the protocol.
• •Pre-menopausal women must have a negative pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant, double barrier and/or complete abstinence (non-periodic).
• •Washout period prior to Day 1 Cycle 1:
• •* ≥ 3 weeks since last chemotherapy or therapeutic radiation therapy (RT)
• •* ≥ 4 weeks or 3 half-lives since prior antibody-based therapy, whichever is shorter
• •* ≥ 2 weeks since any oral anti-neoplastic or oral investigational agent
• •* Resolution of treatment-related toxicity to ≤ grade 1; alopecia and cutaneous toxicity are allowed ≤ grade 2.
• •* ≥1 week since palliative RT
• •Ability to understand and the willingness to sign a written informed consent document.