cancer malignancy
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. Hepatic function as defined by serum bilirubin </= 1.5 x ULN, ALAT and ASAT </= 2.5 x ULN;d. 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
Exclusion criteria
Exclusion criteria: 1. Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up;2. Women who are pregnant or breast feeding. ;3. Both men and women 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. 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, St. Johns wort or macrolide antibiotics as erythromycin and clarithromycin. ;5. Uncontrolled infectious disease or known HIV-1 or HIV-2 type patients;6. Unresolved (>grade 1) toxicities of previous chemotherapy excluding alopecia;7. Bowel obstructions or motility disorders that may influence the absorption of drugs;9. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity;10. Pre-existing neuropathy greater than CTC grade 1;11. Symptomatic cerebral or leptomeningeal metastases;12. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • To determine the maximum tolerated dose (MTD) of docetaxel (as ModraDoc001 10 mg capsules) that can safely be administered in combination with ritonavir to patients with cancer in a bi-daily weekly schedule. | — |
Secondary
| Measure | Time frame |
|---|---|
| • To determine the systemic exposure of the bi-daily ModraDoc001 10 mg capsules in combination with ritonavir. • To determine the hematological and non-hematological toxicity profile of oral docetaxel in combination with ritonavir. • To preliminary assess anti-tumor activity of docetaxel. • To determine the systemic exposure of the novel oral docetaxel formulation (ModraDoc003 10 mg tablets) in combination with ritonavir. • To determine the systemic exposure of the novel oral docetaxel-ritonavir co-formulation (ModraDoc004 10/50 mg tablets). • To determine the effect of co-formulating docetaxel with ritonavir on the systemic exposure of docetaxel. • To determine the inter- and intrapatient variability in plasma pharmacokinetics of docetaxel and ritonavir of ModraDoc001 10 mg capsules in combination with ritonavir, ModraDoc003 10 mg tablets in combination with ritonavir and ModraDoc004 10/50 mg tablets. • 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 the systemic exposure of the oral docetaxel formulation (ModraDoc005 tablets) in combination with ritonavir. • To determine dose limiting toxicities (DLT) and recommended dose (RD) of docetaxel (ModraDoc005 tablets) that can safely be administered to patients with cancer in a bi-daily weekly schedule. • To determine the systemic exposure of the oral docetaxel formulation (ModraDoc006 tablets) in combination with ritonavir. • To determine dose limiting toxicities (DLT) and recommended dose (RD) of docetaxel (ModraDoc006 tablets) that can safely be administered to patients with cancer in a bi-daily weekly schedule. | — |
Countries
Netherlands
Outcome results
None listed