Ph II Cabazitaxel DD Liposarcoma

Study Overview
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Brief Summary
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Soft tissue sarcomas (STS) are a rare group of malignant heterogenous tumors (> 50 histological subtypes, including liposarcoma, the commonest subtype of STS) with distinct genetic, pathological and clinical profiles, and varying patterns of tumor spread. The optimal cytotoxic treatment for this group of patients remains uncertain. Single agents which are most effective include doxorubicin and ifosfamide, but objective response rates and progression-free survival times remain modest. There is clearly a need to improve treatment options for liposarcoma. Eribulin, a antimicrotubule agent that targets the protein tubulin in cells, interfering with cancer cell division and growth , has demonstrated activity in STS. Therefore, it is reasonable to explore whether other anti-microtubule agent like cabazitaxel have a role in STS. Cabazitaxel has been shown to be a relatively safe, effective and tolerated. This drug has been approved by FDA for prostate cancer. The main objective of this trial is to determine whether cabazitaxel demonstrate sufficient antitumor activity for liposarcoma.

Official Title
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Phase II Trial of Cabazitaxel in Metastatic or Inoperable Locally Advanced Dedifferentiated Liposarcoma

Conditions
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Dedifferentiated Liposarcoma

Intervention / Treatment
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* Drug: Cabazitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Local diagnosis of dedifferentiated liposarcoma Age 18-75 yrs WHO performance status 0-1 Radiological or histological diagnosis of inoperable locally advanced or metastatic disease, with evidence of disease progression within the past 6 months 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). Adequate haematological, renal and hepatic function Birth control measures Estimated life expectancy > 3 months Related adverse events from previous therapies ≤ Grade 1 Written informed consent Exclusion Criteria: More than 1 prior molecularly targeted therapy (e.g. CDK4 inhibitor). Any prior such therapy must be completed at least 4 weeks before randomization. Symptomatic CNS metastases Previous encephalopathy of any cause or other significant neurological condition Concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4/5 Pregnancy inflammation of the urinary bladder (cystitis) Other invasive malignancy within 5 years (exceptions 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 Uncontrolled severe illness or medical condition, other than DD liposarcoma Hypersensitivity to taxanes or their excipients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabazitaxel<br>INN: Cabazitaxel 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. | Drug: Cabazitaxel<br> <br> * Other names: Jevtana;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The primary endpoint will be progression free survival, assessed at 12 weeks after start of treatment | 3 years from first patient in | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | 3 years from first patient in | 
| Progression free survival |  | 3 years from first patient in | 
| Overall survival |  | 3 years from first patient in | 
| Objective tumor response | Objective tumor response as defined by RECIST 1.1 | 3 years from first patient in | 
| Time to onset of response | Time to onset of response will be measured for patients achieving an objective response | 3 years from first patient in | 
| Duration of response | Duration of response will be measured for patients achieving an objective response | 3 years from first patient in | 
| Occurence of adverse events | This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting. | 3 years from first patient in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dedifferentiated liposarcoma, cabazitaxel