Primary:* To compare overall survival (OS) in subjects with advanced soft tissue sarcoma ([STS], one of two subtypes: adipocytic [ADI] or leiomyosarcoma [LMS]) when treated with eribulin (Arm A) or dacarbazine (Arm B).Secondary:* To compare…
ID
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall survival, measured from the date of randomization until date of death
from any cause. Subjects who are lost to follow-up and the subjects who are
alive at the date of data cut-off will be censored at the date the subject was
last known alive.
Secondary outcome
Secondary Endpoints:
* Progression-free survival, defined as the time from the date of randomization
to the date of first documentation of disease progression, or date of death
(whichever occurs first). Progression free survival censoring rules will
apply, and will be defined in the SAP.
* Progression-free rate at Week 12, defined as the proportion of subjects alive
and progression-free at 12 weeks from the date of randomization.
* Clinical Benefit Rate, the proportion of subjects who have best overall
response of CR + PR + dSD.
Exploratory Endpoints:
* Objective response rate, the proportion of subjects who have overall response
of CR and PR.
* Disease control rate, the proportion of subjects who have best overall
response of CR + PR + SD.
* Durable Stable Disease, defined as the proportion of subjects who have the
duration of SD *11 weeks.
* Quality of Life Scores, measured using the QLQ C30 and EQ-5D questionnaires.
Overige evaluatiecriteria:
* Pharmacokinetic
* Pharmacodynamic
* Relationship between pharmacokinetic and pharmacodynamic
* Safety
* Assessment of quality of life
Background summary
Approximately half of all STS subjects with intermediate or high-grade tumors
develop metastatic disease requiring systemic treatment. The median survival of
subjects that develop metastases is approximately 12 months, and only a small
subgroup of these subjects achieve long term survival.
Anthracyclines are the first-line therapy for advanced disease. Response rates
of * 20% has been reported with doxorubicin alone or in combination with
ifosfamide, however the median overall survival of patients with metastatic STS
has not improved beyond 12 months. While the majority of patients receive first
line chemotherapy for advanced STS, the rate of delivery of later lines of
therapy falls quickly after failure of first line therapy. Of those patients
receiving adjuvant or first line chemotherapy, approximately half will receive
a 2nd line regimen. There is limited clinical data to support the selection of
the best treatment options in second-line.
Eribulin has demonstrated activity in advanced STS in an EORTC Phase 2 study.
In this trial the Efficacy and Safety of Eribulin is studied, compared with
Dacarbazine.
Study objective
Primary:
* To compare overall survival (OS) in subjects with advanced soft tissue
sarcoma ([STS], one of two subtypes: adipocytic [ADI] or leiomyosarcoma [LMS])
when treated with eribulin (Arm A) or dacarbazine (Arm B).
Secondary:
* To compare progression-free survival (PFS) between Arm A and Arm B.
* To compare progression-free rate at Week 12 (PFR12wks) between Arm A and Arm
B.
* To compare the clinical benefit rate ([CBR], complete response (CR), partial
response (PR) + durable stable disease ([dSD], duration of stable disease (SD)
* 11 weeks) between Arm A and Arm B.
* To compare the safety and tolerability between Arm A and Arm B.
* To characterize the population pharmacokinetics (PK) of eribulin in subjects
with STS.
Exploratory:
* To compare:
- Overall response rate ([ORR] CR and PR),
- Disease control rate ([DCR], CR + PR + stable disease [SD]),
- dSD,
between Arm A and Arm B.
* To explore the relationship between exposure to eribulin and pharmacodynamic
biomarkers and efficacy.
* To explore the relationship between exposure to eribulin and adverse events.
* To investigate and identify blood and tumor biomarkers which can be
correlated with safety and efficacy endpoints.
* To compare quality of life (QoL) scores between Arm A and Arm B.
Study design
This is a Randomized, Open-label, Multicenter, Phase 3 Study
Intervention
Arm A: eribulin mesylate 1.4 mg/m2, as an IV bolus infusion over 2-5 minutes
on Days 1 and 8 of every cycle, where the duration of each cycle is 21 days.
Arm B: dacarbazine 850 mg/m2, or 1,000 mg/m2, or 1,200 mg/m2 (depending on the
subject*s clinical status), IV infusion over 15-30 minutes on Day 1 of every
cycle, where the duration of each cycle is 21 days.
Study burden and risks
Assuming a maximum estimated participation period of approximately 10 months
(screening, baseline, 14 cycles & end of treatment):
- 14x comprehensive physical examination (incl. neurological examination)
- 5x symptom-directed physical exam
- 22x vital signs
- 16x weight
- 1x length
- 30x ECG
- 20x blood sample
- 15x urine collection
- 6x tumour assessment (MRI/CT)
- 2x bone scan
- 17x quality-of-life questionnaires
Also refer to table 2 and 3 of the protocol for a complete overview of the
study visits and procedures.
The most common side effects and risks of Eribulin are: leucopenia,
neutropenia, anemia, thrombocytopenia, periferal neuropathy, nausea, vomiting,
diarrhea, constipation, headache, joint pain and muscle pain, hair loss, loss
of appetite, elevated temperature.
Less common side effects of Eribulin are: gastrointestinal problems,
respiratory problems, infections, depression and insomnia, elevated liver
function test, decrease of potassium, magnesium and phosphate, dehydration,
increase of glucose, increased heart rate, dry mouth, eyes watering, nose
bleed, fluid retention, weight loss and dizziness, tinnitus, interstitial lung
disease, angioedema, kidney failure, dysuria, haematuria, proteinuria, deep
vein thrombosis and pulmonary embolism, allergic reactions.
European Knowledge Centre, Mosquito Way
Hatfield AL10 9SN, Hertfordshire
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European Knowledge Centre, Mosquito Way
Hatfield AL10 9SN, Hertfordshire
GB
Listed location countries
Age
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 adipocytic or leiomyosarcoma, incurable by surgery and/or radiotherapy.
3. Subjects should have received standard therapies for advanced soft tissue sarcoma which must have included an anthracycline (unless contraindicated) with or without ifosfamide and then at least one additional regimen after failure of the anthracycline.
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:
a. 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.
b. Lesions that have had radiotherapy must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
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 any investigational agent within 30 days, 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 participated in a study with eribulin (whether treated with eribulin or not).
4. Radiation therapy encompassing > 30% of bone marrow.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-024483-17-NL |
| ClinicalTrials.gov | NCT01327885 |
| CCMO | NL36010.018.11 |