Randomized phase II trial of cabazitaxel or prolonged infusional ifosfamide in metastatic or inoperable locally advanced dedifferentiated liposarcoma

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 13

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint will be progression free survival, assessed at 12 weeks<br /><br>after start of treatment. Progression will be defined according to RECIST 1.1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints will include<br /><br>* Time to progression<br /><br>* Progression free survival<br /><br>* Overall survival<br /><br>* Objective tumor response as defined by RECIST 1.1 (Ref. 20) where the<br /><br>dedifferentiated component is targeted for measurements of local disease<br /><br>(section 7.5.1.1)<br /><br>* Objective tumor response as defined by RECIST 1.1 where both well<br /><br>differentiated and dedifferentiated components are included in measurements of<br /><br>local disease (measurements to be performed by central review only)<br /><br>* Time to onset of response (for patients achieving an objective response)<br /><br>* Duration of response (for patients achieving an objective response)<br /><br>* Safety (CTCAE Version 4.0)</p><br>