A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

Prior systemic therapy for advanced or metastatic disease (neoadjuvant therapy followed by surgical resection and adjuvant therapy permitted). Palliative radiotherapy to non-target lesions is allowed if completed at least two weeks prior to study entry

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). Palliative radiotherapy to non-target lesions is allowed, is completed at least two weeks prior to study entry.

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

What this study is about