E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced dedifferentiated liposarcoma |
|
E.1.1.1 | Medical condition in easily understood language |
Locally advanced liposarcoma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073135 |
E.1.2 | Term | Dedifferentiated liposarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to determine whether cabazitaxel demonstrates 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 in a phase III setting. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal exclusion criteria |
Registration step 2
-inflammation of the urinary bladder (cystitis)
-symptomatic CNS metastases
-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
-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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after of treatment |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints will include
- Time to progression
- Progression free survival
- Overall survival
- Objective tumor response as defined by RECIST 1.1 (Ref. 20) where the
dedifferentiated component is targeted for measurements of local
disease
- 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)
- Time to onset of response (for patients achieving an objective
response)
- Duration of response (for patients achieving an objective response)
- Safety (CTCAE Version 4.0) |
|
E.5.2.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have either stopped protocol treatment, or have been treated for at least 12 weeks and an evaluation of the disease has been performed
2. The trial is mature for the analysis of the primary end-point as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |