Prostate cancer
Conditions
Interventions
Addition of treatment with ModraDoc006/ritonavir to the standard treatment with
radiotherapy and hormonal therapy.
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologically proven prostate cancer. 2. All eligible patients have hormone naïve non-metastatic radiographic node positive (>4 nodes) high risk prostate cancer. 3. High risk prostate cancer will be defined as node positive with all of the following primary tumour characteristics: Tumour stage >=cT2c and Gleason score >=4+3, any PSA 4. Age above 18 years 5. No signs of metastatic disease on standard diagnostic scans. 6. Adequate haematological, renal and hepatic functions 7. WHO performance status of 0-2 8. For Phase 1A only: Able and willing to undergo blood sampling for PK and PD analysis; 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 give written informed consent
Exclusion criteria
Exclusion criteria: 1. Any treatment with investigational drugs, chemotherapy or immunotherapy within 30 days prior to receiving the first dose of investigational treatment; Patients may be on ADT as long as this is has not been longer than 12 weeks prior the start of the radiotherapy. 2. Patients who have had prior pelvic radiation therapy 3. Patients who have had prior treatment with taxanes 4. TURP within 3 months before start of the study 5. Patients who have had a prostatectomy. 6. Any contra-indication for MRI 7. Major difficulties for marker implantation 8. 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) 9. Unresolved (> grade 1) toxicities of previous chemotherapy, excluding alopecia. 10. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients; 11. Patients with a known history of hepatitis B or C; 12. Bowel obstructions or motility disorders that may influence the resorption of drugs as judged by the treating physician 13. 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 analoga, or St. John*s wort. 14. Pre-existing neuropathy greater than NCI-CTCAE v4.03 grade 1. 15. 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. 16. Legal incapacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose (MTD) of ModraDoc006/r (as ModraDoc006 10 mg tablets in combination with one tablet of 100 mg ritonavir) that can safely be administered in a bi-daily weekly schedule in combination with high-dose intensity modulated radiation therapy and androgen-deprivation therapy (ADT) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the safety profile of ModraDoc006/r in combination with ADT and high dose radiotherapy by looking closely at - Acute toxicity: severity, duration and relation with treatment of all adverse events according to NCI-CTCAE version 4.03 and /or the RTOG acute radiation morbidity scoring criteria occurring from start of treatment until 3 month after end of radiotherapy. - Late toxicity: severity, duration and relation with treatment of all adverse events according to NCI-CTCAE version 4.03 and /or the RTOG late radiation morbidity scoring criteria occurring from 3 months until 1 year after end of radiotherapy. 2. To preliminary assess anti-tumour activity of ModraDoc006/r in combination with radiotherapy and ADT 3. To explore the feasibility and toxicity profile of use of ModraDoc006/r 4. In part 1A: To determine the pharmacokinetics (PK) of docetaxel in this regime. | — |
Countries
Netherlands
Outcome results
None listed