The primary aim of this study is to determine the utility of TOPO2A as a biomarker for sensitivity to doxorubicin or its derivatives. Patients whose planned therapy is doxorucibin or doxil single agent may be enrolled into this trial. In light of its recent FDA approval and differing mechanism of action, patients receiving olaratumab along with doxorubicin will be eligible for this study.

Doxorucibin will be administered at standard 21-day intervals. Doxil will be administered at standard 28-day intervals. Response to therapy will be assessed using standard RECIST criteria every 2 cycles. Patients will continue on study until disease progression, prohibitive toxicity or completion of cumulative dose of 450 mg/m2 of either agent. Overall survival will be assessed every 3 months for 1 year, every 6 months in year 2 and, annually until death.

Inclusion Criteria:

• Patients must consent to providing tumor tissue prior to initiation of therapy if sufficient archival tissue is not available. Archival tissue is permitted if no other anticancer treatment was given after the tissue was obtained (not including surgery or radiation). If a biopsy is required, the treating physician should ensure that this can be done safely.

• Patients with STS will be eligible for the trial if their next planned chemotherapy will include single agent doxorubicin or doxil. Patients who will be receiving concomitant therapy with olaratumab will be allowed to participate.

• Sarcoma subtypes of angiosarcoma, epithelioid sarcoma, leiomyosarcoma, fibrosarcoma, myxofibrosarcoma, synovial sarcoma, pleomorphic rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, liposarcoma (excluding well-differentiated) and malignant peripheral nerve sheath tumor will be included. These are subtypes for which a targeted therapy is not standard of care. All other subtypes will be included on a case by case basis as determined by the principle investigator.

• ≥ 18 years of age.

• Ability to understand and willingness to sign a written informed consent and HIPPA document

• Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields or progressed within a previous radiation field).

• Life expectancy of at least 3 months.

• All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose. Post-menopausal women must meet the criteria of 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >35 mIU/ml (IU/L).

• Patients must have normal organ and marrow function as defined below

  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
  • AST/ALT (SGOT/SGPT) ≤ 3 X institutional normal limits; if liver metastases are present then ≤ 5 X ULN are allowed

Exclusion Criteria:

• Patients may not be receiving any other investigational agents, chemotherapy, radiation therapy or hormonal therapy (i.e. aromatase inhibitors for leiomyosarcoma), with the exception of olaratumab
• Pregnant or breast feeding women.
• Any concomitant medical issue that in the opinion of the treating physician would confound survival from sarcoma (e.g. other active cancer, symptomatic brain metastases, cardiac conditions).

Patients whose planned therapy is doxorucibin or doxil single agent may be enrolled into this trial.