E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic castration-resistant prostate cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Prostate cancer spread to other parts of the body |
|
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 compare progression free survival (PFS) between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients. |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the time to PSA progression between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients. 2. To compare overall survival between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients. 3. To compare the time to pain progression between treatment with cabazitaxel and darolutamide versus treatment with cabazitaxel in mCRPC patients. 4. To evaluate the safety of treatment with docetaxel or cabazitaxel and darolutamide in mCRPC patients. 5. To investigate the relationship between tumour hallmarks at baseline and treatment response 6. To investigate alterations in tumour hallmarks between different timepoints: 7. To investigate the predictive value of potential response markers. 8. To investigate the prognostic value of (changes in) circulating tumour cell (CTC) quantity. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years; 2. A confirmed diagnosis of progressive mCRPC (progression according to Prostate cancer Working Group (PCWG) 3 criteria, castration defined as castrate levels of testosterone of <0.5 ng/mL) with an indication for docetaxel or cabazitaxel. 3. Patients should have had disease progression previously on at least one ARSi (abiraterone, apalutamide, darolutamide or enzalutamide). ARSi administration is allowed both in the mCNPC and in the mCRPC setting. Co-administration of docetaxel in mCNPC (triplet-therapy) is allowed. 4. WHO performance ≤ 1 (see appendix A) 5. Able and willing to sign the Informed Consent Form prior to screening evaluations 6. Adequate haematological, renal and liver function and chemistry.
|
|
E.4 | Principal exclusion criteria |
1. Impossibility or unwillingness to take oral drugs 2. Hypersensitivity to taxanes 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, serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases) 4. Symptomatic peripheral neuropathy CTCAE grade ≥2 5. Docetaxel-rechallenge.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The main study endpoint is progression free survival, which is defined as time from randomization to radiologic, biochemical or pain progression or death from any cause, whichever occurs first, according to PCWG3 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
According to clinical practice by regular follow-up OR at the study cut-off date. |
|
E.5.2 | Secondary end point(s) |
1. Overall survival, defined as time from randomization to death from any cause. 2. Time to progression, defined as time from randomization to radiologic, biochemical or pain progression, whichever occurs first. 3. The time to PSA progression, defined as time from randomization to biochemical progression. 4. The time to pain progression, defined as time from randomization to pain progression. 5. The number and severity of adverse events 6. Cell-free DNA aneuploidy scores and somatic aberrations in circulating tumor DNA 7. CTC-count. 8. Differential expression of relevant genes.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
According to clinical practice by regular follow-up OR at the study cut-off date. |
|
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |