Phase 3 Study to Compare the Efficacy and Safety of Eribulin With Dacarbazine in Subjects With Soft Tissue Sarcoma

Inclusion Criteria

• •1. Histologically confirmed diagnosis of soft tissue sarcoma of high or intermediate grade with one of the following histological subtypes:
• •* Adipocytic sarcoma, including:
• •* Dedifferentiated
• •* Myxoid
• •* Round Cell
• •* Pleomorphic - Leiomyosarcoma
• •2. Documented evidence of advanced (locally recurrent, locally advanced and/or metastatic) adipocytic (restricted to subtypes listed in Inclusion 1) or leiomyosarcoma, incurable by surgery and/or radiotherapy.
• •3. Subjects should have received at least two standard systematic regimens for advanced soft tissue sarcoma one of which must have included an anthracycline (unless contraindicated).
• •4. Radiographic evidence of disease progression by RECIST criteria on or after the last anti-cancer therapy within the 6 months prior to randomization.
• •5. Presence of measurable disease meeting the following criteria:
• •* At least one lesion of greater than or equal to 1.0 cm in long-axis diameter for non lymph nodes or greater than or equal to 1.5 cm in short-axis diameter for lymph nodes which is serially measurable according to RECIST 1.1 using either computerized tomography or magnetic resonance imaging or panoramic and close-up color photography.
• •* Lesions that have had radiotherapy must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
• •6. Eastern Cooperative Oncology Group, performance status of 0, 1 or 2.
• •7. Adequate renal function defined as calculated creatinine clearance greater than 50 mL/min per the Cockroft and Gault formula.
• •8. Adequate bone marrow function, defined as:
• •* Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 or greater than or equal to 1.5 x 10\^9/L.
• •* Platelet count greater than or equal to 100,000/mm3 or greater than or equal to 100 x 10\^9/L.
• •* Hemoglobin (Hb) greater than or equal to 10g/dL at baseline (blood transfusions,hematopoietic growth factors and hematinics are allowed during the Prerandomization Phase to correct Hb values less than 10g/dL).
• •9. Adequate liver function, defined as:
• •* Bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
• •* Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN. For total ALP greater than 3 times ULN, the ALP liver isoenzyme must be less than or equal to 3 times ULN.
• •10. All female subjects will be considered to be of child-bearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation greater than or equal to 1 menstrual cycle prior to randomization, or have undergone a hysterectomy and/or bilateral oophorectomy).
• •Female subjects of child-bearing potential must agree to use two forms of highly effective contraception from the last menstrual period prior to randomization (or use a double barrier method as described below until they are on two forms of highly effective contraception for at least one menstrual cycle), during the study treatment, and for 3 months after the final dose of study treatment. Female subjects exempt from this requirement are subjects who practice total abstinence. If currently abstinent, the subject must agree to use a double barrier method of contraception, i.e., condom and occlusive cap (diaphragm or cervical/vault caps) with spermicide or until they are on two forms of highly effective contraception for at least one menstrual cycle if they become sexually active during the study treatment and for 3 months after the final dose of study treatment. Highly effective contraception includes:
• •* Placement of intrauterine device or system,
• •* Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault cap) with spermicide,
• •* Established hormonal contraceptive methods: oral, injectable or implant. Female subjects who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product from the last menstrual period prior to randomization, and must continue to use the same hormonal contraceptive product during study treatment, and for 3 months after the first dose of study treatment.
• •* Vasectomized partner with confirmed azoospermia.
• •11. Male subjects and their female partner who are of child-bearing potential (as defined in Inclusion 10), and are not practicing total abstinence, must agree to use two forms of highly effective contraception from the last menstrual period of their female partner prior to randomization (or use a double barrier method as described above until they are on two forms of highly effective contraception for at least one menstrual cycle), during study treatment, and for 3 months (or 6 months if they received dacarbazine) after the final dose of study treatment. If currently abstinent, must agree to use a double barrier method of contraception if they become sexually active, or until they are on two forms of highly effective contraception as described above.
• •12. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
• •13. Males or females aged greater than or equal to 18 years at the time of informed consent.