A Randomized, Phase 3, Multicenter, Open-Label Study Comparing TH-302 in Combination with Doxorubicin vs. Doxorubicin Alone in Subjects with Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma
To evaluate the efficacy of TH-302 in combination with doxorubicin as determined by overall survival in subjects with locally advanced unresectable or metastatic soft tissue sarcoma previously untreated with chemotherapy compared with doxorubicin alone. To assess the safety of TH-302 in combination with doxorubicin. To evaluate the efficacy of TH-302 in combination with doxorubicin as determined by progression-free survival and response rate.
Patient must be at least 15 years of age and willing and able to understand the purposes and risks of the study and has signed an informed consent. Patient must have pathologically confirmed diagnosis of soft tissue sarcoma of one of the following types: synovial sarcoma, high grade fibrosarcoma, undifferentiated sarcoma; sarcoma not otherwise specified (NOS), liposarcoma, leiomyosarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, pleomorphic rhabdomyosarcoma, myxofibrosarcoma, epithelioid sarcoma, undifferentiated pleomorphic sarcoma/MFH, other soft tissue sarcomas for which doxorubicin is appropriate first line therapy. Patient must have locally advanced unresectable or metastatic disease with no standard curative therapy and for whom treatment with single agent doxorubicin is considered appropriate. Patient must have measurable disease. Patient must be up and out of bed at least 75% of the time and have good blood counts and good organ function. Patients who have had prior systemic therapy for advanced or metastatic soft tissue sarcoma will be excluded (patients who have had neoadjuvant therapy followed by surgical resection and adjuvant therapy are permitted). Patients who have had prior treatment with ifosfamide, cyclophosphamide, anthracyclines, or anthracenediones are excluded. Patients with seizure disorder requiring anticonvulsant therapy, unless seizure-free for the last year, will be excluded. Patients with known brain metastases will be excluded (unless previously treated and well controlled for a period of at least 3 months). Patients with severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation less than 90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia will be excluded.
After signing and dating and informed consent document, patient will be screened for eligibility to determine if it is safe to enroll onto trial. After review of all test results for eligibility, patient will be enrolled onto the study. This treatment regimen is administered in the Outpatient Clinic. Patients will be randomized (like the flip of a coin) to receive either TH-302 plus Doxorubicin or Doxorubicin alone. Each cycle is 21 days in length. Patients randomized to receive TH-302 plus Doxorubicin will receive TH-302 on Day 1 and 8 of every 21-day cycle with Doxorubicin on Day 1 only. Patients randomized to receive Doxorubicin alone, will receive this drug on Day 1 ONLY of each 21 day cycle. Patients will be required to have either a Central Venous Catheter or Infusa-Port placed prior to initiating treatment on this trial. Patients will be required to return to clinic for frequent blood work and tests as well as doctor and nurse visits. Strict adherence to study visits and requirements is of utmost importance in order to ensure the safety of all patient participants.
12/11/2013 04:02 AM