Inclusion Criteria: - Male or female ≥ 15 years of age - Ability to understand the purposes and risks of the study and has signed or, if appropriate, the subject's parent or legal guardian has signed a written informed consent form approved by the investigator's IRB/Ethics Committee - Pathologically confirmed diagnosis of soft tissue sarcoma of the following histopathologic types: - Synovial sarcoma - High grade fibrosarcoma - Undifferentiated sarcoma; sarcoma not otherwise specified (NOS) - Liposarcoma - Leiomyosarcoma (excluding GIST) - Angiosarcoma (excluding Kaposi's sarcoma) - Malignant peripheral nerve sheath tumor - Pleomorphic Rhabdomyosarcoma - Myxofibrosarcoma - Epithelioid sarcoma - Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (MFH) (including pleomorphic, giant cell, myxoid and inflammatory forms) - Locally advanced unresectable or metastatic disease with no standard curative therapy available and for whom treatment with single agent doxorubicin is considered appropriate. - Recovered from reversible toxicities of prior therapy - Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Life expectancy of at least 3 months - Acceptable liver, renal, hematological and cardiac function - All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception Exclusion Criteria: - Prior systemic therapy for advanced or metastatic disease (neoadjuvant therapy followed by surgical resection and adjuvant therapy permitted) - Low grade tumors according to standard grading systems - Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards - Prior therapy with an anthracycline or anthracenedione - Prior mediastinal/cardiac radiotherapy - Current use of drugs with known cardiotoxicity or known interactions with doxorubicin - Anti-cancer treatment with radiation therapy, neoadjuvant or adjuvant chemotherapy, targeted therapies, immunotherapy, hormones or other antitumor therapies within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C) - Significant cardiac dysfunction precluding treatment with doxorubicin - Seizure disorders requiring anticonvulsant therapy unless seizure-free for the last year - Known brain metastases (unless previously treated and well controlled for a period of ≥ 3 months) - Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years - Severe chronic obstructive or other pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia - Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery - Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy - Prior therapy with a hypoxic cytotoxin - Subjects who participated in an investigational drug or device study within 28 days prior to study entry - Known infection with HIV, hepatitis B, or hepatitis C - Subjects who have exhibited allergic reactions to a structural compound similar to TH-302,doxorubicin or their excipients - Females who are pregnant or breast-feeding - Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study - Unwillingness or inability to comply with the study protocol for any reason