SAKK 08/16 Erhaltungstherapie mit Darolutamid (ODM 201) bei Patienten mit fortgeschrittenem Prostatakarzinom, die bereits mit neuartigen hormonalen Medikamenten behandelt wurden

Drug: ODM-201;Other: Placebo

Gender: Male
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

- Written informed consent according to Swiss law and ICH/GCP regulations before
registration and prior to any trial specific procedures not part of normal medical
care.

- Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate

- Castration resistance: tumor progression after orchiectomy or during treatment with
GnRH analogues (agonists or antagonists)

- Metastatic disease, documented by imaging

- Total testosterone = 50 ng/dL (= 1.7 nmol/L)

- Treatment with abiraterone AND/OR enzalutamide for at least 8 weeks prior to taxane
based chemotherapy

- No evidence of disease progression after chemotherapy with docetaxel (at least
cumulative dose of = 300 mg/m2 or total dose = 600mg) or cabazitaxel (at least
cumulative dose of = 80 mg/m2 or total dose = 160 mg)

- No evidence of progression on imaging according to PCWG3

- No evidence of progression on PSA levels referred to the nadir since start of
taxane treatment (PSA progression defined as > 25% increase of PSA level or >50%
if PSA decrease under chemotherapy >50% AND > 5 ng/mL increase in the absolute
PSA value)

- Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or
antagonists) during the trial

- Planned start of trial treatment 2 to 8 weeks after last taxane dose

- Male patient 18 years or older

- WHO performance status of =2

- Laboratory values as specified below

- alanine aminotransferase (ALT) = 2.5 x ULN (except for patients with liver
metastases = 5.0 x ULN)

- Total bilirubin = 1.5 x ULN (except for patients with Gilbert's disease = 3.0 x
ULN)

- Estimated creatinine clearance using the Cockcroft-Gault formula > 30 mL/minute

- Blood counts at screening: haemoglobin = 90 g/L, absolute neutrophil count =
1500/?l (1.5x109/L), platelet count = 100,000/?l (100x109/L) (patient must not
have received any growth factor or blood transfusion within 7 days of the
haematology laboratory obtained at screening)

- Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) = 40% as
determined by echocardiography (ECHO)

- Patient is able and willing to swallow trial drug as whole tablet

- Sexually active male subjects must agree to use condoms as an effective barrier method
and refrain from sperm donation, and/or their female partners of reproductive
potential to use a method of effective birth control, during the study treatment and
for 3 months after the end of the treatment.

- Patient agrees to participate in the mandatory translational research project

Exclusion Criteria:

- Prior chemotherapy for prostate cancer except from chemotherapy with a taxane

- Concurrent disease requiring higher doses of corticosteroid than the equivalent of 10
mg prednisone per day

- Known CNS or leptomeningeal metastases

- Clinical or radiological evidence of current spinal cord compression

- History of hematologic or primary solid tumor malignancy, unless in remission for at
least 2 years from registration with the exception of localized non-melanoma skin
cancer or carcinoma in situ having undergone complete resection.

- Prior therapy for mCRPC with modern anti-hormonal treatment except for enzalutamide or
abiraterone

- Concurrent treatment with other experimental drugs or treatment in a clinical trial
within 30 days prior to trial entry (except clinical trial SAKK 96/12)

- Concomitant use of other anti-cancer drugs or radiotherapy except for local pain
control and GnRH analogues

- Severe or uncontrolled cardiovascular disease

- Acute exacerbations of chronic illnesses, serious infections, or major surgery within
4 weeks before expected start of treatment

- ECG abnormalities of Q-wave infarction, unless identified = 6 months prior to
registration or QTc interval >480 msec

- Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI
absorption or tolerance of ODM-201

- Known hypersensitivity to trial drug or to any component of the trial drug

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.