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
Protocol serial number	N07DOW
Sponsor	The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/ALH) (Netherlands)
Funder	The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/ALH) (Netherlands)

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

Plesmanlaan 121
Amsterdam
1066CX
Netherlands

Email	j.slijkerman@nki.nl

Study information

Primary study design	Interventional
Study design	Optimal dosing study
Secondary study design	Non randomised controlled trial
Study type	Participant 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
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Docetaxel, ritonavir
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	31/12/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	78
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

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes