ModraDoc006/r in Metastatic Castration-resistant Prostate Cancer

Inclusion Criteria: 1. Histological or cytological proven castration-resistant metastatic prostate cancer with an indication for systemic treatment with intravenous docetaxel at the discretion of the physician 2. Progressive disease defined as biochemical and/or radiological progression according to the Prostate Cancer Working group 3 recommendations. 3. Disease evaluable for biochemical and/or radiological response (in case disease is measurable the RECIST 1.1 criteria and the guidelines for measurement of bone lesions according to the Prostate Cancer Clinical Trials Working Group 3 will be applied, as described in "Efficacy assessment"). 4. Chemotherapy naïve patients. Prior treatment with abiraterone or enzalutamide as first line therapy is allowed. In case of use of enzalutamide, this should be stopped 2 weeks before the first ModraDoc006/r intake. For patients that have used enzalutamide, altered pharmacokinetic sampling should be done, as described at 'Pharmacokinetics and Circulating Tumour Cell measurements" 5. Castrate levels of testosterone, defined as ≤ 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L) 6. Age equal or above 18 years 7. Adequate haematological, renal and hepatic functions 8. WHO performance status of 0-2 9. Life expectancy above 3 months allowing adequate follow up of toxicity evaluation and antitumor activity; 10. Able and willing to swallow oral medication 11. Able and willing to undergo blood sampling 12. Able and willing to give written informed consent Exclusion Criteria: 1. Any treatment with investigational drugs, chemotherapy or immunotherapy within 28 days prior to receiving the first dose of investigational treatment. Palliative radiotherapy is allowed before and during the study as long as this is scheduled outside the DLT-period (first 28 days) and at least 4 days after intake of study medication and no intestinal toxicity is expected from the radiotherapy. 2. Patients with symptomatic brain metastases. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant therapy for at least 6 weeks are allowed to enroll. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT completed at screening, demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive anti-epileptic drugs or corticosteroid treatment indicated for brain metastasis. Patients with a history of leptomeningeal metastases are not eligible. 3. Unreliable contraceptive methods. Men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms) 4. Unresolved (\> grade 1) toxicities of previous therapy, excluding alopecia. 5. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients; 6. Patients with a known history of hepatitis B or C; 7. Bowel obstructions or motility disorders that may influence the resorption of drugs as judged by the treating physician 8. Concomitant use of MDR and CYP3A modulating drugs such as Ca+- entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications, other protease inhibitors, (non) nucleoside analogues, or St. John's wort. 9. Use of Bicalutamide within 14 days prior to receiving the first dose of investigational treatment 10. Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance; Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications. 11. Legal incapacity