Metastatic Castration Resistant Prostate Cancer MedDRA version: 14.1 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10036920 Term: Prostate cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 1003690
Conditions
Interventions
Trade Name: Cabazitaxel
Product Name: Jevtana
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Current Sponsor code: L01CD04
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Karolinska University Hospital
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Written informed consent • Histological confirmed prostate cancer • Macroscopic metastatic disease • Prior treatment with Docetaxel • Castration resistant disease defined as : Serum testosterone (=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: • Less than 21 days since prior treatment with chemotherapy, • Less than 14 days since radiotherapy or surgery to the start of cabazitaxel • Less than 4 weeks after stopping abiraterone or other new anti-hormonal drugs • Prior isotope therapy or radiotherapy to > 30% of bone marrow (whole pelvic radiotherapy is not an exclusion criteria) • Adverse events from previous cancer therapies > grade 1 (NCI CTCAE V4.03) with the exception of alopecia. (With respect to peripheral neuropathy grade 2 is acceptable) • Age less than 18 years • ECOG performance status > 2 • Known CNS malignancy • Within 6 months of randomization: myocardial infarction , unstable angina, angioplasty, bypass surgery, stroke, TIA, or congestive heart failure NYHA class III or IV • Within 3 months prior to randomization: treatment resistant peptic ulcer disease, infectious or inflammatory bowel disease, pulmonary embolism • Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results • Unable to comply with study procedures • History of hypersensitivity to docetaxel or polysorbate 80 • Inadequate organ and bone marrow function as defined below • Concurrent or planned treatment with potent inhibitors or inducers of cytochrome P450 3A4/5 ( eg simvastatin, keotconazole. For comprehensive list please see Appendix ) a one week wash out period is necessary for patients who are already on these treatments). • Patients with reproductive potential not implementing accepted and effective method of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if a weekly regime improves tolerability of cabazitaxel compared to the standard 3 week regimen;Secondary Objective: To compare drug efficacy, drug safety and patient quality of life in a weekly and three week scheduling of cabazitaxel;Primary end point(s): The primary endpoint is to compare dose intensity of the 3-weekly and the weekly schedules after 18 weeks of planned therapy. The defininition of dose intensity is based upon the total dose the patient actually receives in relation to the total dose that the patient is expected to receive by 18 weeks of therapy. This definition applies to patients discontinuing therapy for reasons other than disease progression. For patients stopping treatment due to lack of efficacy, dose-intensity is based on the total dose received over the interval of time from the start of chemotherapy until the date of the last dose given. Both treatment arms are designed to have the same dose-intensity at the outset ie 150 mg/m2 as the total dose given over 18 weeks representing 100 % dose intensity in relation to the planned total dose at the start of treatment. Dose delays, dose reductions and especially stopping treatment for reasons other than disease progression will be mirrored by lowering the dose given in relation to the dose planned and as such is an objective measure of drug tolerability. ;Timepoint(s) of evaluation of this end point: By definition all patients discontinuing treatment before 18 weeks from the start of therapy or patients who reach 18 weeks of therapy will be evaluated for the primary endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival Disease Specific Survival Progression Free Survival Progression free survival is defined as the length of time from randomization to the first documentation of one of the following: PSA progression or Pain progression or Death due to any cause or Radiological disease progression PSA progression is defined as either a 25% increase (at least 2 ng/ml) from baseline in patients not achieving a prior > 50% decrease in PSA or a 50% increase in PSA (at least 2 ng/ml) above the nadir value in patients who have achieved a prior > 50% decrease in PSA. A confirmatory PSA will be taken at least 3 weeks later. During the first twelve weeks of therapy increases in PSA may reflect treatment induced PSA-flare and can therefore be misleading. A rising PSA, during the first 12 weeks of treatment, without clinical and/or radiological signs of progression is therefore not considered as disease progression. Pain will be assessed using the Present Pain Intensity (PPI) scale (see appendix). Pain assessment will be made at baseline and before each treatment until the patient discontinues therapy. Diaries will be used to assess analgesic consumption. Pain progression is defined as 1) the need for palliative radiotherapy if the symptoms giving rise to radiotherapy were not present at baseline or 2) they were present but the pain have worsened to the extent that the physician in question feels that it is in the patients best interest to radiate. Pain progression exists when the patients` 3) median PPI score increases by at least one point from nadir or 4) there is an increase in analgesic consumption of 25% over baseline. Radiological disease progression and tumour response are defined according to Recist 1.1 criteria. If lesions are present only in bone and assessed by bone scan, size and intensity of target lesions may not be used to determine disease progression. The appearance of two new lesions confirmed six weeks later | — |
Countries
Sweden
Contacts
Public ContactClinical Trials Unit
Stockholm Läns Landsting
Outcome results
None listed