Randomized phase II trial of cabazitaxel or prolonged infusional ifosfamide in metastatic or inoperable locally advanced dedifferentiated liposarcoma
- Conditions
- ocally advanced dedifferentiated liposarcomaMedDRA version: 16.1Level: PTClassification code 10073135Term: Dedifferentiated liposarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003672-39-IT
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
- Local diagnosis of dedifferentiated liposarcoma
- Mandatory availability for shipment of formalin-fixed, paraffin-embedded, 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
- 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 non-melanoma 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main 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 patients with metastatic or inoperable locally advanced dedifferentiated (DD) liposarcoma to justify further investigation of the efficacy of these treatment options in a phase III setting.;Secondary Objective: Not applicable;Primary end point(s): Progression free survival;Timepoint(s) of evaluation of this end point: 12 weeks after randomisation
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary endpoints will include<br>- Time to progression<br>- Progression free survival<br>- Overall survival<br>- 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)<br>- 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)<br>- Time to onset of response (for patients achieving an objective response)<br>- Duration of response (for patients achieving an objective response)<br>- Safety (CTCAE Version 4.0);Timepoint(s) of evaluation of this end point: Progression and response related end-points will be assessed by CT/MRI every 12 weeks during treatment. Survival will be assessed every 12 weeks after the end of treatment. Safety will be assessed at each visit.