BOLD-100 Plus Doxorubicin in Advanced Soft Tissue Sarcomas

Prior treatment

• Radiation (except planned or ongoing palliative radiation outside of the region of measurable disease), chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy.
• Major surgery within 4 weeks before initiation of therapy.
• Prior systemic therapy.
• Active, ongoing or uncontrolled active infection within one week prior to first dose.
• Malignancies other than disease under study within 2 years prior to Cycle 1, Day 1, except for those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). Prior chemotherapy is allowed apart from regimens that contained anthracycline based therapies.
• Concurrent therapy with approved or investigational anticancer therapeutic agents.

Other illness

• Unstable cardiovascular function:
  • symptomatic ischemia, or.
  • uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmic is excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded) or.
  • congestive heart failure (CHF) of NYHA Class ≥3, or.
  • myocardial infarction (MI) within 3 months of initiation of therapy.
• Known to be HIV seropositive.
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B virus (HBV) surface antigen (HBsAg).
• Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
• Serious psychiatric or medical conditions that could interfere with treatment.
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results.

Other

• Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
• Patient is pregnant or lactating.

• Written informed consent in accordance with federal, local, and institutional guidelines.
• Age \> 18 years.
• Patients must have histologically confirmed locally advanced/unresectable or metastatic soft tissue sarcoma of limited subtype LMS, DDLPS and UPS (including Myxofibrosarcoma-MFS).
• Patients be systemic treatment naïve, with incurable, advanced or metastatic disease.
• Patient must have measurable disease as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematopoietic function:
  • total white blood cell (WBC) count ≥2000/mm3.
  • absolute neutrophil count (ANC) ≥1500/mm3.
  • platelet count ≥100,000/mm3.
• Adequate hepatic function:
  • Bilirubin \<2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 times ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 X ULN. In the case of known (radiological and/or biopsy documented) liver metastasis, ALT/AST \<5.0 X ULN is acceptable.
• Adequate renal function defined as \<1.5x upper limits of normal
• Cardiac function: A normal left ventricular ejection fraction (LVEF) of \> 50% as evidenced by an echocardiogram or nuclear medicine study performed within 28 days of the proposed study commencement.
• Female patients of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at 72 hours prior to receiving the first dose of study medication. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.