Soft Tissue Sarcoma
Conditions
Interventions
One Arm (eribulin mesylate 1.4 mg/m2 intravenous): Administration of eribulin mesylate at a dose of 1.4 mg/m2 as an intravenous bolus infusion over 2-5 minutes on days 1 and 8 of every cycle, where th
Drug
E02.319
D02.925.200
Sponsors
Eisai Inc.
Eisai Inc.
Eligibility
Age
18 Years to No maximum
Inclusion criteria
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 and 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. Participants 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 Response Evaluation Criteria In Solid Tumors (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: a. At least one lesion of greater than or equal to 1.0 centimeter (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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either computerized tomography or magnetic resonance imaging or panoramic and close-up color photography. b. Lesions that have had radiotherapy must show evidence of progressive disease based on Response Evaluation Criteria in Solid Tumors (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 milliliter per minute (mL/min) as per the Cockroft and Gault formula. 8. Adequate bone marrow function, defined as: a. Absolute neutrophil count (ANC) greater than or equal to 1,500/cubic millimeter (mm3) or greater than or equal to 1.5 x 10^9/Liter (L). b. Platelet count greater than or equal to 100,000/mm3 or greater than or equal to 100 x 10^9/L. c. Hemoglobin (Hb) greater than or equal to 10 grams per deciliter (g/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: a. Bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert’s syndrome. b. 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 participants 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 participants 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 pa
Exclusion criteria
Exclusion criteria: 1. Participants who have received any anti-cancer therapy, including radiotherapy, cytotoxic, hormonal, biological (including humanized antibodies) and targeted agents within 21 days, or five half-lives of the drug (whichever is longer) prior to randomization. 2. Participants who have not recovered from acute toxicities as a result of prior anti-cancer therapy to less than or equal to Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for peripheral neuropathy (see Exclusion 6) and alopecia. 3. Participants that have previously been treated with dacarbazine or its analogue temozolomide or eribulin. 4. Major surgery within 21 days prior to randomization. 5. Pre-existing peripheral neuropathy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 2. 6. Significant cardiovascular impairment, defined as: a. Cardiac failure, New York Heart Association (NYHA) Class II according to the NYHA Functional Classification. b. Unstable angina or myocardial infarction within 6 months of enrolment. c. Serious and potentially life-threatening arrhythmia. 7. Participants with a high probability of Long QT (Q wave and T wave) Syndrome or QTc (corrected QT) interval prolongation of more than or equal to 501 msec on at least two separate electrocardiograms (ECGs), following correction of any electrolyte imbalance. 8. Participants with known central nervous system metastases. 9. Any serious concomitant illness or infectious disease requiring treatment, or infectious disease not requiring treatment, but with significant risks for myelosuppressive complications associated with chemotherapy. 10. Any malignancy that required treatment, or has shown evidence of recurrence (except for soft tissue sarcoma, non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 5 years prior to randomization. 11. Female participants must not be pregnant as documented by a negative beta-human chorionic gonadotropin (beta-hCG) test with a minimum sensitivity 25 international units /Liter (IU/L) or equivalent unit of beta-hCG at Screening and Baseline, or breastfeeding. 12. Hypersensitivity to the active substance, or any of the excipients of the eribulin drug product, or dacarbazine, (please refer to the dacarbazine prescribing information). 13. Any medical or other condition which, in the opinion of the principal investigator or designee, will preclude participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is overall survival. Overall survival is defined as the time in months from the date of randomization to the date of death, regardless of cause. In the absence of confirmation of death, the participants will be censored either at the date that participant was last known to be alive or the date of study cut-off, whichever is earlier. The overall survival will be compared between the two treatment arms using a two-sided stratified log-rank test. The overall survival will be summarized using Kaplan-Meier estimates by treatment arm. Greenwood's formula will be used for the standard error of the Kaplan-Meier estimate in the calculation of the confidence limits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration in months of progression-free survival (PFS) from the date of treatment start (day 1) to the date of first documentation of disease progression, or date of death (whichever occurs first). Disease progression was defined as at least a 20 percent increase in the sum of the longest diameter of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions assessed using Response Evaluation Criteria In Solid Tumors (RECIST). | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, India, Israel, Italy, Netherlands, New Zealand, Poland, Republic of Korea, Romania, Russian Federation, Singapore, Spain, Thailand, United Kingdom, United States
Contacts
Public ContactDavid Adamo
Eisai Inc.
Outcome results
None listed