Metastatic Castration Resistant Prostate Cancer MedDRA version: 17.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Zytiga
Product Name: ZYTIGA 250 mg tabletter
Pharmaceutical Form: Tablet
Trade Name: Jevtana
Product Name: JEVTANA 60 mg koncentrat och vätska till infusionsvätska, lösning
Pharmaceutical
Sponsors
Umeå University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent 2. Histological confirmed prostate cancer 3. Macroscopic metastatic disease previous treated with docetaxel 4. Castration resistant disease defined as: a) Plasma testosterone (=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: 1. Less than 4 weeks since prior treatment with chemotherapy, 2. Less than 4 weeks days since radiotherapy or surgery to the start, bone pain palliative radiotherapy is allowed 3. Less than 4 weeks after stopping endocrine therapies including anti-androgen. 4. No “new drugs” (ie abiraterone, enxalutamide, Ra223 and other) given in mCRPC stage will be allowed to ensure that the trial is strictly second line after Docetaxel. 5. Prior isotope therapy or radiotherapy to > 30% of bone marrow (whole pelvic radiotherapy is not an exclusion criteria) 6. Use of other investigational drug therapy for any reason is prohibited. 7. Persistent adverse events from previous cancer therapies > grade 1 (NCI CTCAE V4.03) with the exception of alopecia. (With respect to nail changes grade 2 is acceptable) 8. Symptomatic peripheral neuropathy grade >2 (NCI CTCAE] v.4.03. 9. Age less than 18 years 10. ECOG performance status > 2 11. Known CNS malignancy 12. Within 6 months of randomization: myocardial infarction , unstable angina, angioplasty, bypass surgery, stroke, TIA, or congestive heart failure NYHA class III or IV 13. Within 3 months prior to randomization: treatment resistant peptic ulcer disease, infectious or inflammatory bowel disease, pulmonary embolism 14. 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 15. Unable to comply with study procedures 16. Patients with reproductive potential not implementing accepted and effective method of contraception. 17. History of severe hypersensitivity reaction (=grade 3) to docetaxel 18. History of severe hypersensitivity reaction (=grade 3) to polysorbate 80 containing drugs 19. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus) 20. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix A and B) 21. Inadequate organ and bone marrow function as evidenced by: a) Hemoglobin 1.5 x ULN; e) Total bilirubin >1 x ULN, 22. Serum creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate if tumor expression levels of the biomarker AKR1C3 can predict mCRPC patient PSA response to therapy with abiraterone or cabazitaxel, during the first treatment period.;Secondary Objective: I. To evaluate if tumor expression levels of the biomarker AR-V7 can predict mCRPC patient PSA response to therapy with abiraterone or cabazitaxel, during the first treatment period. II. Investigate if baseline tumor expression levels of AR-V7 and AKR1C3 can be used to select what sequence of treatment (abi+cab vs cab+abi) is most likely to result in successful treatment. III. Investigate if treatment with abiraterone and or cabazitaxel result in different resistance mechanisms with respect to induction of AR splice variants or other resistance mechanisms. IV. Validate tissue markers in bloodbased entities (“liquid biopsies”) such as Exosomes, Trombocytes and Circulating Tumor Cells (CTCs). V. Comparison of PSA progression free survival, Radiologic progression free survival in relation to assigned first treatment according to biomarker status and overall survival in relation to both treatment periods according to biomarker status. VI. Safety;Primary end point(s): The proportion of patients with PSA response = 50% after treatment with Abiraterone or Cabazitaxel in the first treatment period before cross over comparing groups defined by AKR1C3 levels as high or low at baseline ;Timepoint(s) of evaluation of this end point: At progression after the first treatment period before cross over. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): I. The proportion of patients with PSA response = 50% after treatment with Abiraterone or Cabazitaxel in the first treatment period before crossover comparing groups defined by AR-V7 presence or abscence at baseline. II. The summary of the combined PSA progression free survival in the two treatment periods comparing groups defined by the combined AKR1C3 and AR-V7 patterns at baseline and sequence of treatments. III. The proportion of patients that have low expression of AR-V7 at baseline and who develops high expression during therapy with Abiraterone differs compared to corresponding group that receives Cabazitaxel as measured at first progression. IV. Blood based expression of biomarkers correlates to tissue based expression of the same markers. V. Progression free survival endpoints a. PSA and radiological PFS, b. Overall survival VI. Safety VII. Exploratory endpoints • Search for new biomarkers • Improvement in Pain Control • Quality of Life /FACT_P) • BSI (Bone Scan Index) in relation to PCGW2;Timepoint(s) of evaluation of this end point: I. At progression after the first treatment period before cross over. II. End of study III. At progression after the first treatment period before cross over IV. End of study V. End of study VI. During the study VII. During the study | — |
Countries
Sweden
Contacts
Public ContactSponsor
Umeå University Hospital
Outcome results
None listed