advanced cancer
Conditions
Interventions
None listed
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of cancer;2. Patients for whom no standard therapy of proven benefit exist;3. Patients who might benefit from treatment with docetaxel, e.g. advanced breast, gastric, esophagus, bladder, ovarian cancer and non-small cell lung cancer, head and neck cancers, prostate cancer and carcinoma of unknown primary site. ;4. Age > 18 years;5. Able and willing to give written informed consent;6. Able and willing to undergo blood sampling for pharmacokinetics;7. Life expectancy > 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity;8. Minimal acceptable safety laboratory values;a. ANC of > 1.5 x 109 /L;b. Platelet count of > 100 x 109 /L;c. Hepd. Renal function as defined by serum creatinine < 1.5 x ULN or creatinine clearance > 50 ml/min (by Cockcroft-Gault formula).;9. WHO performance status of </= 2;10. No radio- or chemotherapy within the last 4 weeks prior to study entry (palliative limited radiation for pain reduction is allowed);11. Able and willing to swallow oral medication;atic function as defined by serum bilirubin < 1.5 x ULN, ALAT and ASAT < 2.5 x ULN;12. Arm F: Patients for whom weekly paclitaxel can seriously be considered therapy with palliative intent, with tumortypes that reasonably will respond.
Exclusion criteria
Exclusion criteria: 1. Patients with known alcoholism, drug addiction and/or a history of psychotic disorders that are not suitable for adequate follow up;2. Women who are pregnant or breast feeding. ;3. Both men and women who do not agree to use a reliable contraceptive method throughout the study ;4. Concomitant use of MDR and CYP3A modulating drugs such as Ca¬¬+-entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors, (non) nucleoside analoga, or St. Johns wort.;5. Uncontrolled infectious disease or known HIV-1 or HIV-2 type patients;6. Unresolved (>grade 1) toxicities of previous chemotherapy;7. Bowel obstructions or motility disorders that may influence the resorption of drugs;9. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity;10. Symptomatic cerebral or leptomeningeal metastases;11. Acid neutralizing medicines (e.g. aluminium hydroxide), should not be administered for at least 2 hours prior to and after the intake of ketoconazol (Arm D)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and optimal dose for oral docetaxel/ritonavir that can safely be administered to patients with cancer as monotherapy in a weekly schedule. | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine the hematologic and non-hematologic toxicity. To preliminary assess anti-tumor activity of docetaxel and paclitaxel To determine the PK of oral docetaxel and paclitaxel To establish the effect of functional genetic polymorphisms in genes encoding for Pgp, MRP2, OATP1B3, CYP3A4, CYP3A5 and CYP2C8 To determine the effect of the timing and dose of RTV on the PK of docetaxel. To determine the systemic exposure of the new capsule formulation of docetaxel, with or without coating, in combination with ritonavir. To investigate whether the systemic exposure to docetaxel can also be enhanced by other CYP3A4 inhibitors, especially ketoconazole, grapefruit juice and claritromycin. To preliminary investigate whether the systemic exposure to paclitaxel can also be enhanced by CYP3A4 inhibitors; ritonavir, ketoconazole, or claritromycin To preliminary determine the systemic exposure of the new oral pacltiaxel formulation with or without an eneric coating in combination with ritonavir | — |
Countries
Netherlands
Outcome results
None listed