E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic castration-resistant prostate cancer |
Gemetastaseerde castratie-resistente prostaatkanker |
|
E.1.1.1 | Medical condition in easily understood language |
Prostate cancer spread to other parts of the body |
Uitgezaaide prostaatkanker |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the influence of darolutamide on the pharmacokinetics of cabazitaxel compared to cabazitaxel alone in mCRPC patients. |
Het bepalen van de invloed van darolutamide op de farmacokinetiek van cabazitaxel vergeleken met enkel cabazitaxel bij patiënten met mCRPC |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of cabazitaxel and darolutamide combination therapy, by means of PSA response, compared to baseline. 2. To study the pharmacokinetic profile of darolutamide. 3. To evaluate the safety of cabazitaxel and darolutamide combination therapy. |
1. Evalueren van de werkzaamheid van cabazitaxel en darolutamide combinatiebehandeling, door middel van PSA respons ten opzichte van baseline |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years; 2. Patients with a confirmed diagnosis of mCRPC with an indication for cabazitaxel treatment at the standard dose of 20 mg/m2. 3. WHO performance ≤ 1. 4. Able and willing to sign the Informed Consent Form prior to screening evaluations 5. Adequate baseline patient characteristics (complete blood count, serum biochemistry which involves sodium, potassium, creatinine, calculation of creatinine clearance, AST, ALT, gamma glutamyltranspeptidase, lactate dehydrogenase, ALP, Total bilirubin, Albumin, glucose) |
1. Leeftijd ≥ 18 jaar; 2. Patiënten met een bevestigde mCRPC diagnose met een indicatie voor behandeling met cabazitaxel in de standaard dosis van 20mg/m2. 3. WHO performance ≤ 1. 4. Het Informed Consent Formulier kunnen en willen tekenen vooraf aan screenende onderzoeken. 5. Adequate baseline karakteristieken. (volledig bloedbeeld, bloedchemie met o.a. natrium, kalium, kreatinine, GFR, ASAT, ALAT, gGT, LDH, ALP, totaal bilirubine, albumine, glucose) |
|
E.4 | Principal exclusion criteria |
1. Use of (over the counter) medication or (herbal) supplements which can interact with either cabazitaxel or darolutamide, e.g. by induction or inhibition of CYP3A4 or P-gp. Dexamethasone and prednisone are allowed. 2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) 3. Known serious illness or medical unstable conditions that could interfere with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or herpes zoster, organ transplants, kidney failure (GFR<60), serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases) 4. Treatment with abiraterone, enzalutamide, apalutamide or darolutamide six weeks prior to day 1 of the study. |
1. Gebruik van (handverkoop) medicatie of (kruiden)supplementen die een interactie hebben met cabazitaxel of darolutamide, b.v. door inductie of inhibitie van CYP3A4, P-gp. Dexamethasone en prednison zijn toegestaan. 2. Patiënten met bekende verlaagde medicijnabsorptie (b.v. gastrectomie en achloorhydrie) 3. Patiënten met een onderliggend ziektebeeld of medisch instabiele conditie, hetgeen kan interfereren met de interventie in deze studie (bijvoorbeeld HIV, hepatitis, Varicella Zoster of herpes zoster, orgaan transplantaties, nierfalen (GFR<60 ml/min/1.73 m2), een serieuze leverziekte (o.a. ernstige levercirrose), cardiale en respiratoire ziekten) 4. Behandeling met abirateron, enzalutamide, apalutamide of darolutamide in de zes weken voorafgaand aan dag 1 van de studie. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
AUC of cabazitaxel |
AUC van cabazitaxel |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Other pharmacokinetic parameters of cabazitaxel, including clearance (CL), maximum concentration (Cmax), time to maximum concentration (Tmax) and half-life (t½). 2. Pharmacokinetic parameters of darolutamide, including AUC, CL, Cmax, Tmax and t½. 3. The incidence and severity of side-effects during treatment with cabazitaxel and darolutamide. 4. PSA response, as defined by the difference between PSA levels after combination treatment with cabazitaxel and darolutamide and PSA levels at baseline. |
1. Andere farmacokinetische parameters van cabazitaxel, inclusief klaring (CL), maximale concentratie (Cmax), tijd tot maximale concentratie (Tmax) en halfwaardetijd (t½). 2. Farmacokinetische parameters van darolutamide, inclusief AUC, CL, Cmax, Tmax en t½. 3. De incidentie en ernst van bijwerkingen tijdens behandeling met cabazitaxel en darolutamide. 4. PSA respons, gedefinieerd door het verschil tussen PSA na combinatiebehandeling met cabazitaxel en darolutamide en PSA op baseline. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of the study |
Einde van de studie |
|
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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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 | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
|
LVLS |
Laatste visite van de laatste patiënt |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |