To determine the effect of a high-fat meal on the exposure to docetaxel given as ModraDoc006 tablets in combination with ritonavir in patients with cancer.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effect of a high-fat meal on the exposure to docetaxel given
as ModraDoc006 tablets in combination with ritonavir in patients with cancer.
Secondary outcome
- To assess the safety of weekly ModraDoc006/ritonavir treatment
- To establish the effect of functional genetic polymorphisms on the
pharmacokinetics of oral docetaxel and ritonavir.
Background summary
In two phase I studies the combination of oral ModraDoc006 (docetaxel) in
combination with ritonavir is investigated. In these trials the maximum
tolerated dose was determined. The anti-tumor activity and exposure to
docetaxel warranted further development of the compound ModraDoc006.
Since further development is planned there is a need for a food-effect study to
investigate the effect food administration has on the exposure to docetaxel.
This study is designed as a worst-case scenario in which a high fat meal is
co-administered with oral docetaxel / ritonavir. There is a known food-effect
for docetaxel therefore an effect on the exposure to docetaxel is expected.
Study objective
To determine the effect of a high-fat meal on the exposure to docetaxel given
as ModraDoc006 tablets in combination with ritonavir in patients with cancer.
Study design
Open label, cross-over, food-effect study of ModraDoc006/ritonavir.
Intervention
Patients will be treated with weekly oral docetaxel and ritonavir for two
weeks. Patients will be asked to come after a fasting period. On one day the
will need to consume a high-fat breakfast. On the other day the will remain
fasted until several hours after treatment.
During this period an intravenous catheter will be placed for pharmcokinetics.
Study burden and risks
Patients are at risk for docetaxel and ritonavir related toxicity.
Patients will be admitted twice for one night for collection of pharmacokinetic
samples. These samples will be drawn from an intravenous catheter, which will
be placed twice. Patients will be asked to come to the hospital twice for
additional pharmacokinetic sampling.
Patients are at risk of side-effects of the blood draw.
Louwesweg 6
Amsterdam 1066 EC
NL
Louwesweg 6
Amsterdam 1066 EC
NL
Listed location countries
Age
Inclusion criteria
1. Histological or cytological proof of cancer;2. Patients for whom no standard therapy of proven benefit exists ;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 or older;5. Able and willing to give written informed consent;6. Able and willing to undergo blood sampling for pharmacokinetics;7. Life expectancy more than 3 months;8. Minimal acceptable safety laboratory values;8.1. Hb >= 6.0 mmol/l;8.2. ANC >= 1.5 x 109 /L;8.3. Platelet count >= 100 x 109 /L;8.4. Serum bilirubin >= 1.5 x ULN, ALAT and ASAT >= 2.5 x ULN (or >= 5 x ULN in case of presence of liver metastases);8.5. Serum creatinine < 1.5 x ULN or creatinine clearance >= 50 ml/min (by Cockcroft-Gault formula).;9. WHO performance status of >= 1 ;10. No radio- or chemotherapy within the last 4 weeks prior to first dose of study medication (palliative radiation on limited field for pain reduction is allowed);11. Able and willing to swallow oral medication.
Exclusion criteria
1. Patients with known alcoholism, drug addiction and/or psychotic disorders in the medical history that are not suitable for adequate follow up;2. Women who are pregnant or breast-feeding. ;3. Men and women, who do not agree to use two reliable contraceptive methods throughout the study (adequate contraceptive methods are: use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom, diaphragm with spermicide, male sterilization, true abstinence). ;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 analogs, St. Johns wort or macrolide antibiotics like erythromycin and clarithromycin. ;5. Uncontrolled infectious disease or known HIV-1 or HIV-2 infection;6. Unresolved (>grade 1) toxicities of previous chemotherapy, excluding alopecia;7. Bowel obstructions or motility disorders or previous surgery that may influence the absorption of drugs;8. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity;9. Pre-existing neuropathy greater than CTC grade 1;10. Patients with suspected or known brain metastases, unless they have been adequately treated and are asymptomatic without use of corticosteroids (for at least 1 month) ;11. 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2016-001234-10-NL |
CCMO | NL57240.031.16 |