Condition category
Cancer
Date applied
11/11/2010
Date assigned
10/01/2011
Last edited
10/01/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Jan Schellens

ORCID ID

Contact details

Plesmanlaan 121
Amsterdam
1066CX
Netherlands
j.slijkerman@nki.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N07DOW

Study information

Scientific title

Weekly administration of oral docetaxel in combination with ritonavir for the treatment of a variety of tumour types: an optimal dosing study

Acronym

N07DOW

Study hypothesis

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

Local Medical Ethics Committee approved on the 11th of October 2007

Study design

Optimal dosing study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details below to request a patient information sheet

Condition

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 names

Docetaxel, ritonavir

Primary outcome measures

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 trial start date

01/10/2007

Overall trial end date

31/12/2010

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Total approx. 78 (Arm A: 30 approx; Arms B-C: 6 per arm; Arms D-L: 4 per arm)

Participant 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)

Recruitment start date

01/10/2007

Recruitment end date

31/12/2010

Locations

Countries of recruitment

Netherlands

Trial participating centre

Plesmanlaan 121
Amsterdam
1066CX
Netherlands

Sponsor information

Organisation

The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/ALH) (Netherlands)

Sponsor details

Plesmanlaan 121
Amsterdam
1066CX
Netherlands
j.slijkerman@nki.nl

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research organisation

Funder name

The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/ALH) (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes