Phase ll trial of cabazitaxel in metastatic or inoperable locally advanced dedifferentiated liposarcoma

Registration step 1
-Local diagnosis of DD liposarcoma.
-Mandatory availability for shipment of formalin-fixed, paraffin-embedded, tumor-containing tissue blocks from primary tumor and/or metastatic site. lnformation on previous histopathology reports and previous molecular analysis will be entered in an electronic CRF, to accompany the tissue sample(s).
-lf a block cannot be provided, the following should be submitted:
EORTC-1202-STBSG Ph ll Cabazitaxel DD liposarcoma Version 3.0 22/75 May 10, 2016
-For cases that will be reviewed in UK (refer to chapter 15.3): 4 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.
-For cases that will be reviewed in France (refer to chapter 15.3): 3 x 4 micron sections on unstained (coated) slides for FISH and 15 unstained slides (4 micron) for immunohistochemistry.
-Before patient registration step 1, 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.;Registration step 2
-Central pathology confirmation of DD liposarcoma within 3 weeks after registration step 1.
-Radiological or histological diagnosis of inoperable locally advanced or metastatic disease, with evidence of disease progression within the past 6 months prior to registration step 2.
-Clinically and/or radiographically documented measurable disease within 28 days prior to registration step 2.
At least one site of disease must be unidimensionally measurable according to RECIST 1.1
-Note: as DD liposarcoma commonly arises on a background of well differentiated liposarcoma, and as the latter well differentiated element can remain stable for prolonged periods without therapy, we recommend that when defining radiological measurable or target lesions per RECIST 1.1, specially in the region of the primary tumor mass if present, these should be chosen to include specifically the solid or higher density elements of the disease (which tend to correlate pathologically with the DD element), and not the low density fatty elements of the disease, which tend to correlate with the well differentiated element.
-One previous chemotherapy regimen for locally advanced or metastatic DD liposarcoma (this could include pre-operative chemotherapy for primary disease).
-Age 18-75 years old
-WHO performance status 0-1
-Adequate haematological, renal and hepatic function
-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 birlh control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
-lt is recommended that patients do not attempt to become pregnant or to breast feed after exposure to these chemotherapy agents, as there is no available data on safety. lf despite this advice patients wish to do so, then it is recommended a minimum of 6 months should first be allowed to elapse from the last received dose.
-Men should use reliable contraception throughout treatment and are recommended to continue this for up to 6 months after the last dose of cabazitaxel.
-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.

Registration step 2
-more than 1 prior molecularly targeted therapy (e.9. CDK4 inhibitor). Any such prior therapy must be completed at least 2-4 weeks prior to registration step 2.
-inflammation of the urinary bladder (cystitis)
-symptomatic CNS metastases. lf 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.
-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 DD liposarcoma
-concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A415 (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)