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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01327885




Registration number
NCT01327885
Ethics application status
Date submitted
31/03/2011
Date registered
4/04/2011
Date last updated
12/03/2018

Titles & IDs
Public title
Phase 3 Study to Compare the Efficacy and Safety of Eribulin With Dacarbazine in Subjects With Soft Tissue Sarcoma
Scientific title
A Randomized, Open-label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of Eribulin With Dacarbazine in Subjects With Soft Tissue Sarcoma
Secondary ID [1] 0 0
E7389-G000-309
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Soft Tissue Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eribulin mesylate 1.4 mg/m^2 intravenous
Treatment: Drugs - Dacarbazine of 850 mg/m^2, or 1,000 mg/m^2, or 1,200 mg/m^2 IV

Experimental: Arm A -

Active Comparator: Arm B -


Treatment: Drugs: Eribulin mesylate 1.4 mg/m^2 intravenous
Administration of eribulin mesylate at a dose of 1.4 mg/m^2 as an intravenous (IV) bolus infusion over 2-5 minutes on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days.

Treatment: Drugs: Dacarbazine of 850 mg/m^2, or 1,000 mg/m^2, or 1,200 mg/m^2 IV
Administration of dacarbazine at a dose of 850 mg/m^2, or 1,000 mg/m^2, or 1,200 mg/m^2 selected by the Principal Investigator [PI] or designee according to the subject's clinical status as an IV infusion over 15-30 minutes on Day 1 of every cycle, where the duration of each cycle is 21 days.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - OS was defined as the time in months from the date of treatment start until death, regardless of cause. In the absence of confirmation of death, participants were censored either at the date that participant was last known to be alive or the date of study cut-off, whichever was earlier. Participants who died on the date of randomization had a survival time of 0.5 day. Allocation of randomization numbers were performed based upon the following stratification factors: (a) Histology (ADI or LMS), (b) Region (Region 1: USA and Canada; or Region 2: Western Europe, Australia, Israel; or Region 3: Eastern Europe, Latin America, and Asia), and (c) Number of prior regimens for advanced soft tissue sarcoma (STS) (2 or >2 prior regimens).
Timepoint [1] 0 0
From date of treatment start until date of death from any cause, assessed up to data cutoff date (02 Jan 2015), for up to approximately 3 years 11 months
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - PFS was defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death (whichever occurred first). The date of disease progression was defined as the date of radiologic disease progression as assessed by the investigator or designee based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Participants who did not have an event (i.e., participants who were lost to follow-up or who did not progress or die at the date of data cut-off), were censored. Participants who discontinued study treatment without disease progression were censored on the date of their last radiological assessment (scan date).
Timepoint [1] 0 0
Randomization (day 1) to the date of first documentation of disease progression, or date of death (whichever occurred first)
Secondary outcome [2] 0 0
Progression-Free Rate at 12 Weeks (PFR12wks) - The PFR12wks was defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. Tumor assessment by the investigator or designee was based on RECIST criteria 1.1.
Timepoint [2] 0 0
From date of treatment start until Week 12
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR) - CBR was defined as the percentage of participants who have best overall response (BOR) of CR, or PR, or duration of stable disease (dSD) greater than or equal to 11 weeks, between Arm A and Arm B. CBR was estimated by treatment arm based on the tumor response evaluation performed by the PI or designee according to RECIST 1.1. CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter.
Timepoint [3] 0 0
From date of treatment start (Day 1) until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff (02 Jan 2015), for up to approximately 3 years 11 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 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. 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 greater than CTCAE Grade 2.

6. Significant cardiovascular impairment, defined as:

- Cardiac failure, New York Heart Association (NYHA) Class II according to the NYHA
Functional Classification,

- 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 imbalance.

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 randomization.

11. Female subjects must not be pregnant as documented by a negative beta-human chorionic
gonadotropin (beta-hCG) test with a minimum sensitivity 25 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 PI or designee, will
preclude participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- St Leonards
Recruitment hospital [3] 0 0
- Woolloongabba
Recruitment hospital [4] 0 0
- Woodville South
Recruitment hospital [5] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- St Leonards
Recruitment postcode(s) [3] 0 0
- Woolloongabba
Recruitment postcode(s) [4] 0 0
- Woodville South
Recruitment postcode(s) [5] 0 0
- Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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California
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Colorado
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Delaware
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District of Columbia
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Florida
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Georgia
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Illinois
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Iowa
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Massachusetts
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Missouri
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San Miguel de Tucuman
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Argentina
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San Salvador de Jujuy
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Austria
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Graz
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Austria
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Salzburg
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Wien
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Belgium
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Bruxelles
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Belgium
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Leuven
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Belgium
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Liege
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Rio Grande Do Sul
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Santa Catarina
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Paris
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France
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Poitiers
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France
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Saint-Priest en Jarez
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France
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Villejuif
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Germany
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Berlin
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Dresden
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Germany
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Essen
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Koln
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Israel
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Pordenone
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Candiolo
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Monza
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Padova
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Italy
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Rozzano (MI)
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Torino
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Korea, Republic of
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Daejeon
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Gliwice
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Craiova
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Romania
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Iasi
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Romania
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Sibiu
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Russian Federation
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Chelyabinsk
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Obninsk
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Singapore
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Singapore
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Spain
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Baleares
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Spain
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Cataluna
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Spain
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Comunidad De Madrid
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Spain
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Barcelona
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Spain
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Valencia
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Thailand
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Songkhla
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Thailand
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Pathum Wan
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United Kingdom
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Glasgow
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
State/province [103] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, open-label, multicenter, Phase 3 study comparing the efficacy and
safety of eribulin with dacarbazine in subjects with advanced soft tissue sarcoma who have
disease progression within 6 months prior to study enrolment following standard therapies
which must have included an anthracycline, unless contraindicated and then at least one
additional regimen after failure of the anthracycline.
Trial website
https://clinicaltrials.gov/show/NCT01327885
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications