Metastatic castration-resistant prostate cancer MedDRA version: 19.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: ModraDoc006
Pharmaceutical Form: Tablet
INN or Proposed INN: DOCETAXEL
CAS Number: 114977285
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 50-60
Tr
Sponsors
Modra Pharmaceuticals B.V.
Eligibility
Sex/Gender
Male
Inclusion criteria
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) 4. Chemotherapy naïve patients. Prior treatment with abiraterone or enzalutamide as first line therapy is allowed. 5. Castrate levels of testosterone 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 10. Able and willing to swallow oral medication 11. Able and willing to undergo blood sampling for pharmacokinetics and assessment of CTCs. 12. Able and willing to give written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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. 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the recommended dose determined as the maximum tolerated dose (MTD) of docetaxel (as ModraDoc006 10 mg tablets) that can safely be administered in combination with ritonavir to patients with metastatic castration-resistant prostate cancer in a bi-daily weekly schedule without interruption.;Secondary Objective: • To determine the systemic exposure of docetaxel and ritonavir given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir. • To determine the hematological and non-hematological toxicity profile of oral docetaxel in combination with ritonavir. • To preliminary assess the anti-tumor activity of oral docetaxel. • To establish the effect of functional genetic polymorphisms in five genes (SLCO1B3, ABCB1, ABCC2, CYP3A4 and CYP3A5) on the pharmacokinetics of oral docetaxel and ritonavir. • To determine dose limiting toxicities (DLT) and recommended dose (RD) of ModraDoc006/r that can safely be administered to patients with metastatic castration-resistant prostate cancer in a bi-daily weekly schedule. ;Primary end point(s): The recommended dose determined as the maximum tolerated dose (MTD) of docetaxel (as ModraDoc006 10 mg tablets) that can safely be administered in combination with ritonavir to patients with metastatic castration-resistant prostate cancer in a bi-daily weekly schedule without interruption.;Timepoint(s) of evaluation of this end point: Safety will be evaluated during the complete treatment of 30 weeks until 28 days after the last treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The systemic exposure of docetaxel and ritonavir given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir. • The hematological and non-hematological toxicity profile of oral docetaxel in combination with ritonavir. • The preliminary anti-tumor activity of oral docetaxel. • The effect of functional genetic polymorphisms in five genes (SLCO1B3, ABCB1, ABCC2, CYP3A4 and CYP3A5) on the pharmacokinetics of oral docetaxel and ritonavir. • The dose limiting toxicities (DLT) and recommended dose (RD) of ModraDoc006/r that can safely be administered to patients with metastatic castration-resistant prostate cancer in a bi-daily weekly schedule.;Timepoint(s) of evaluation of this end point: - Pharmacokinetics and pharmacogenetics will be evaluated after sampling during the first 2 treatment weeks - Safety will be evaluated during the complete treatment of 30 weeks until 28 days after the last treatment - Antitumor activity will be evaluated every 6 weeks. | — |
Countries
Netherlands
Contacts
Public ContactA.M. Bergman
NKI-AVL
Outcome results
None listed