A Randomized, Open-label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of Eribulin With Dacarbazine in Subjects With Soft Tissue Sarcoma
1. Histologically confirmed diagnosis of soft tissue sarcoma of high or intermediate
grade with one of the following histological subtypes:
- Adipocytic sarcoma, including:
- 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
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 ≥ 1.0 cm in long-axis diameter for non lymph nodes or ≥ 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 > 50 mL/min per
the Cockroft and Gault formula.
8. Adequate bone marrow function, defined as:
- Absolute neutrophil count (ANC) ≥ 1,500/mm3 or ≥ 1.5 x 109/L.
- Platelet count ≥ 100,000/mm3 or ≥ 100 x 109/L.
- Hemoglobin (Hb) ≥ 10g/dL at baseline (blood transfusions,hematopoietic growth
factors and hematinics are allowed during the Prerandomization Phase to correct Hb
values < 10g/dL).
9. Adequate liver function, defined as:
- Bilirubin ≤ 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) ≤ 3 times ULN. For total ALP > 3 times ULN, the ALP
liver isoenzyme must be ≤ 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 ≥ 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
- 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
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 ≥ 18 years at the time of informed consent.
1. Subjects 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. Subjects
who have not recovered from acute toxicities as a result of prior anti-cancer therapy to ≤
Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for
peripheral neuropathy (see Exclusion 6) and alopecia.
3. Subjects 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 > CTCAE Grade 2. 6. Significant cardiovascular impairment, defined as:
- Cardiac failure > New York Heart Association (NYHA) Class II according to the NYHA
- Unstable angina or myocardial infarction within 6 months of enrolment,
- Serious and potentially life-threatening arrhythmia. 7. Subjects with a high
probability of Long QT Syndrome or QTc interval prolongation of more than or equal to
501 msec on at least two separate ECGs, following correction of any electrolyte
8. Subjects 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
11. Female subjects must not be pregnant as documented by a negative beta-human
chorionic gonadotropin (ß-hCG) test with a minimum sensitivity 25 IU/L or equivalent
unit of ß-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
13. Any medical or other condition which, in the opinion of the PI or designee, will
preclude participation in a clinical trial.