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

Phase 1

Conditions: ocally advanced dedifferentiated liposarcoma
MedDRA version: 19.0Level: 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-GB

Lead Sponsor: European Organisation for Research and Treatment of Cancer (EORTC)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 50

Inclusion Criteria

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.
-If a block cannot be provided, the following should be submitted:
? For cases that will be reviewed in UK : 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: 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.
-One previous chemotherapy regimen for locally advanced or metastatic DD liposarcoma (this could include pre-operative chemotherapy for primary disease).
-Not more than 1 prior molecularly targeted therapy (e.g. CDK4 inhibitor). Any such prior therapy must be completed at least 2-4 weeks prior to registration step 2.
-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
-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.
-It 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. If 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.
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Registration step 2
-inflammation of the urinary bladder (cystitis)
-symptomatic CNS metastases
-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
-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 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)
-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.

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 demonstrates 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 in the 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 start of treatment

Secondary Outcome Measures

Name	Time	Method
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.;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 <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)

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