Weekly administration of oral docetaxel in combination with ritonavir for the treatment of a variety of tumour types
| ISRCTN | ISRCTN32770468 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN32770468 |
| Secondary identifying numbers | N07DOW |
- Submission date
- 11/11/2010
- Registration date
- 10/01/2011
- Last edited
- 10/01/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Jan Schellens
Scientific
Scientific
Plesmanlaan 121
Amsterdam
1066CX
Netherlands
| j.slijkerman@nki.nl |
Study information
| Study design | Optimal dosing study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details below to request a patient information sheet |
| Scientific title | Weekly administration of oral docetaxel in combination with ritonavir for the treatment of a variety of tumour types: an optimal dosing study |
| Study acronym | N07DOW |
| Study objectives | We aim to determine the optimal dose and formulation of oral docetaxel in combination with ritonavir and investigating if the systemic exposure to docetaxel can also be enhanced by other CYP3A4 inhibitors. Hypothesis: 30 mg oral docetaxel in combination with 100 mg ritonavir is a safe starting dose. |
| Ethics approval(s) | Local Medical Ethics Committee approved on the 11th of October 2007 |
| Health condition(s) or problem(s) studied | Cancer; various docetaxel sensitive-tumours |
| Intervention | 1. Oral and intravenous administration of docetaxel/paclitaxel and CYP3A4 substrates 2. Blood draw for PK and laboratory analasys 3. Computed tomography (CT) every 2 months |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Docetaxel, ritonavir |
| Primary outcome measure | To determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and optimal dose of docetaxel (ModraDOC001) that can safely be administered to patients with cancer in a weekly schedule. |
| Secondary outcome measures | 1. To determine the haematologic and non-haematologic toxicity 2. To preliminary assess anti-tumour activity of docetaxel 3. To determine the effect of ritonavir on the clearance of docetaxel 4. To estimate the apparent oral bioavailability of docetaxel in combination with ritonavir 5. To establish the effect of functional genetic polymorphisms, C1236T (for MDR1) and CYP3A4*1B, on the pharmacokinetics and pharmacodynamics of oral docetaxel and ritonavir 6. To determine the effect of a second ritonavir dose 4 hours post-dose 7. To determine the systemic exposure of the new oral docetaxel formulation (ModraDOC001) in combination with ritonavir 8. To determine the systemic exposure to docetaxel after administration of ModraDOC001 alone. 9. To investigate whether the systemic exposure to docetaxel can also be enhanced by other CYP3A4 inhibitors, especially ketoconazole, grapefruit juice and clarithromycin 10. To investigate whether ritonavir improves the apparent bioavailability of paclitaxel 11. To investigate whether the systemic exposure to paclitaxel can also be enhanced by other CYP3A4 inhibitors, especially ketoconazole, and clarithromycin 12. To determine the systemic exposure of the new oral paclitaxel formulation (ModraPAC001) in combination with ritonavir 13. To preliminary investigate the influence of a double dose of ritonavir 200 mg on the pharmacokinetics of oral docetaxel and paclitaxel |
| Overall study start date | 01/10/2007 |
| Completion date | 31/12/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Total approx. 78 (Arm A: 30 approx; Arms B-C: 6 per arm; Arms D-L: 4 per arm) |
| Key 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, oesophagus, bladder, ovarian cancer and non-small cell lung cancer, head and neck cancers, prostate cancer and carcinoma of unknown primary site 4. Aged greater than or equal to 18 years 5. Able and willing to give written informed consent 6. Able and willing to undergo blood sampling for pharmacokinetics 7. Life expectancy greater than or equal to 3 months allowing adequate follow up of toxicity evaluation and anti-tumour activity 8. Minimal acceptable safety laboratory values 8.1. Absolute neutrophil count (ANC) of greater than or equal to 1.5 x 10^9/L 8.2. Platelet count of greater than or equal to 100 x 10^9/L 8.3. Hepatic function as defined by serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN 8.4. Renal function as defined by serum creatinine less than or equal to 1.5 x ULN or creatinine clearance greater than or equal to 50 ml/min (by Cockcroft-Gault formula) 9. World Health Organisation (WHO) performance status of less than or equal to 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 12. Arm F: Patients for whom weekly paclitaxel can seriously be considered therapy with palliative intent, with tumour types that reasonably will respond |
| Key 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 human immunodeficiency virus (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 (greater than grade 1) toxicities of previous chemotherapy 7. Bowel obstructions or motility disorders that may influence the resorption of drugs 8. Chronic use of H2-receptor antagonists or proton pump inhibitors 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) |
| Date of first enrolment | 01/10/2007 |
| Date of final enrolment | 31/12/2010 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Plesmanlaan 121
Amsterdam
1066CX
Netherlands
1066CX
Netherlands
Sponsor information
The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/ALH) (Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Plesmanlaan 121
Amsterdam
1066CX
Netherlands
| j.slijkerman@nki.nl | |
"ROR" |
https://ror.org/03xqtf034 |
Funders
Funder type
Research organisation
The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/ALH) (Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
