The main objective is to determine whether cabazitaxel or prolonged infusional ifosfamide demonstrate sufficient antitumor activity (as measured by progression free survival at 12 weeks) in pre-treated patients with metastatic or inoperable locally…
ID
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be progression free survival, assessed at 12 weeks
after start of treatment. Progression will be defined according to RECIST 1.1.
Secondary outcome
Secondary endpoints will include
* Time to progression
* Progression free survival
* Overall survival
* Objective tumor response as defined by RECIST 1.1 (Ref. 20) where the
dedifferentiated component is targeted for measurements of local disease
(section 7.5.1.1)
* Objective tumor response as defined by RECIST 1.1 where both well
differentiated and dedifferentiated components are included in measurements of
local disease (measurements to be performed by central review only)
* Time to onset of response (for patients achieving an objective response)
* Duration of response (for patients achieving an objective response)
* Safety (CTCAE Version 4.0)
Background summary
Soft tissue sarcomas have a historical lack of investment in research due to
their rarity but there is a recognized need to improve treatment options
through clinical trials tailored to individual subtypes. In the case of
dedifferentiated liposarcoma, anti-microtubular agents show promise and the
aforementioned index patient*s experience suggests that cabazitaxel, for which
extensive safety data is available, should be formally assessed. Prolonged
infusional ifosfamide also shows promise, with a new way of administering an
established active drug, supported by encouraging responses and safety data
within early case series. The relative paucity of alternative treatment options
with clinically meaningful benefit for this group of patients, who are often
young and fit, has led to the development of this phase II study, assessing
progression-free survival rates at 12 weeks with cabazitaxel, or prolonged
ifosfamide, as second-line treatment in metastatic or inoperable locally
advanced dedifferentiated liposarcoma.
Study objective
The main objective is to determine whether cabazitaxel or prolonged infusional
ifosfamide demonstrate sufficient antitumor activity (as measured by
progression free survival at 12 weeks) in pre-treated patients with metastatic
or inoperable locally advanced DD liposarcoma to justify further investigation
of the efficacy of these treatment options in the phase III setting.
Study design
This trial will be an international, multi-center, open label phase II trial
where patients with metastatic or locally advanced DD liposarcoma will be
randomized between two parallel single agent treatment arms - cabazitaxel or
prolonged infusional ifosfamide.
Crossover is not planned.
Intervention
Patients will be randomized in a 1:1 ratio, stratified by institution,
performance status (0 vs 1) and prior therapy (ifosfamide vs. molecularly
targeted vs. other), to either
* Treatment arm 1: Cabazitaxel will be administered at a dose of 25 mg/m² by
intravenous infusion, over 1 hour, on day 1 of each 21 day cycle. Treatment
should be administered until disease progression, unacceptable toxicity or
patient's refusal.
* Treatment arm 2: Ifosfamide will be administered at a dose of 1 g/m²/day,
along with mesna at 550 mg/m²/day, both as a prolonged intravenous continuous
infusion via a central venous catheter and an appropriate ambulatory infusional
pump (per local institutional policies) for days 1 to 14 of each 28 day
cycle.Treatment will be administered until disease progression, unacceptable
toxicity or patient's refusal.
Study burden and risks
300 minutes per cycle in the ifosfamide treatment arm, 450 minutes per cycle in
the cabazitaxel treatment arm.
The prolonged infusional ifosfamide will be delivered through an ambulatory
pump and central venous catheter in the upper arm for 14 days. This increases
changes of infection and thrombosis. The catheter is treated weekly and
patients receive instructions to prevent infections. In addition, the
ambulatory pump will be changed and turned off during these treatment visits.
Extra blood assessments will be performed compared to regular treatment. This
is three times more frequent per cycle in the ifosfamide treatment arm and two
times more frequent per cycle in the cabazitaxel treatment arm.
Avenue E. Mounier 83/11
Brussel 1200
BE
Avenue E. Mounier 83/11
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
Local diagnosis of dedifferentiated liposarcoma
- Mandatory availability for shipment of formalin-fixed, paraffinembedded, tumor-containing tissue blocks from primary tumor and/or metastatic site. Or if not available: x 1 micron sections on coated slides, one thin H&E stained section and 20 unstained sections of usual thickness (2-4 micron) on coated slides (cases to be reviewed in UK), or, 3 x 4 micron sections on unstained (coated) slides for FISH and 15 unstained slides (4 micron) for immunohistochemistry (cases to be reviewed in France)
- written informed consent for central collection of tissue block or slides and any other trial-specific procedures must be obtained from the patient according to ICH/GCP, and national/local regulations, allowing for collection, storage and analysis of tissue and screening procedures
- Central pathology confirmation is required before starting the patient screening
- Radiological or histological diagnosis of inoperable locally advanced or metastatic disease, with evidence of disease progression within the past 6 months prior to randomization
- Clinically and/or radiographically documented measurable disease within 21 days prior to randomization. At least one site of disease must be unidimensionally measurable according to RECIST 1.1
- One previous chemotherapy regimen for locally advanced or metastatic dedifferentiated liposarcoma (this could include pre-operative chemotherapy for primary disease if subsequent complete resection was not achieved).
- Not more than 1 prior molecularly targeted therapy (e.g. CDK4 inhibitor). Any such prior therapy must be completed at least 4 weeks prior to randomization.
- Age 18-70 years old
- WHO performance status 0-1
- Adequate haematological, renal and hepatic function within 7 days prior to randomization:
Haematology: haemoglobin > 90 g/L or 5.6 mmol/L, absolute granulocytes > 1.5 x 109/L, platelets > 100 x 109/L
Biochemistry: creatinine clearance (CrCl) * > 60 ml/min Hepatic: bilirubin < upper limit of normal (ULN) of institutional limits, ALT and/or AST< 2.5 x ULN, albumin > 30 g/L. If isolated elevated bilirubin < 2 x ULN normal and Gilbert's syndrome suspected, suggest repeating bloods after food. If bilirubin normalizes then this is acceptable.
- Estimated life expectancy > 3 months
- All related adverse events from previous therapies must have recovered to * Grade 1 (except alopecia)
- Women of child bearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
- Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Exclusion criteria
- Inflammation of the urinary bladder (interstitial cystitis), impaired renal function and/or obstructions of the urine flow.
- Symptomatic CNS metastases. If asymptomatic CNS metastases are present these should have been previously treated and stable for at least 3 months and patient should not require maintenance steroids.
- Previous encephalopathy of any cause or other significant neurological condition
- Other invasive malignancy within 5 years, with the exception of nonmelanoma skin cancer, localized cervical cancer, localized and presumably cured prostate cancer or adequately treated basal or squamous cell skin carcinoma.
- significant cardiac disease: i.e. active ischaemic heart disease or cardiac failure (NYHA (Appendix D) > class 1)
- uncontrolled severe illness or medical condition (including acute infection, uncontrolled diabetes), other than the dedifferentiated liposarcoma
- concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments)
- Known hypersensitivity to taxanes or their excipients (cabazitaxel, like docetaxel, is solubilized in polysorbate 80 and ethanol)
- Known hypersensitivity to ifosfamide
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 | EUCTR2012-003672-39-NL |
| ClinicalTrials.gov | NCT01913652 |
| CCMO | NL51542.091.14 |