Safety and Efficacy Study of Glufosfamide in Previously Treated Advanced Soft Tissue Sarcoma

An Open-Label Phase 2 Study of the Efficacy and Safety of Glufosfamide in Previously Treated Advanced Soft Tissue Sarcoma

Primary Objective:

1. To evaluate the efficacy of glufosfamide in subjects with advanced soft tissue sarcoma as measured by objective response rate

Secondary Objectives:

1. To evaluate the efficacy of glufosfamide in subjects with advanced soft tissue sarcoma as measured by duration of response, progression-free survival and overall survival
2. To evaluate the safety of glufosfamide in subjects with advanced soft tissue sarcoma

Exploratory Objectives:

1. To evaluate the biological effect of glufosfamide on the metabolic profile in subjects with advanced soft tissue sarcomas, as determined by FDG-PET
2. To correlate efficacy endpoints with expression of tumor-associated glucose transporter proteins

Inclusion Criteria:

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
• Pathologically confirmed diagnosis of soft tissue sarcoma
• Locally advanced unresectable or metastatic disease with no standard curative therapy available that has progressed since the most recent therapy
• Measurable disease by RECIST criteria with at least one target lesion
• 1 or 2 prior chemotherapy/systemic therapy regimens for advanced disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
• A minimum of 3 weeks between prior chemotherapy, radiation therapy, immunotherapy, or other anti-tumor therapy and study entry
• Recovered from reversible toxicities of prior therapy
• Hemoglobin ≥ 9.0 g/dL, neutrophils ≥ 1,500/µL, platelets ≥ 100,000/µL
• Total bilirubin ≤ 1.5-fold ULN, AST/ALT ≤ 2.5-fold ULN (≤ 5-fold if liver metastases)
• Normal creatinine clearance (≥85 mL/min for men and ≥75 mL/min for women; calculated by Cockcroft-Gault formula
• 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) from entry into the study through 6 months after the last dose

Exclusion Criteria:

• Soft tissue sarcoma of the following subtypes: gastrointestinal stromal tumor (GIST), alveolar soft parts sarcoma, hemangiopericytoma and Kaposi's sarcoma
• Most recent relapse occurring during treatment with ifosfamide within 4 weeks of last dose
• Symptomatic brain or leptomeningeal metastases
• Active clinically significant infection requiring antibiotics
• Recent (one year) history or symptoms of cardiovascular disease (NYHA Class 2, 3, or 4), particularly coronary artery disease, arrhythmias or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, cerebrovascular accident or congestive heart failure
• 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
• Major surgery within 3 weeks of the start of study treatment, without complete recovery
• Females who are pregnant or breast-feeding
• Participation in an investigational drug or device study within 21 days of study entry
• Concomitant disease or condition that could interfere with the conduct of the study, or that in the opinion of the investigator would pose an unacceptable risk to the subject in this study
• Unwillingness or inability to comply with the study protocol for any other reason