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
N98ODO
Study information
Scientific title
Oral bioavailability of docetaxel in combination with cyclosporin A and activity of the combination in advance breast cancer: A randomised controlled trial
Acronym
N98ODO
Study hypothesis
1. The systemic exposure of docetaxel after oral administration of docetaxel in combination with cyclosporin A (CsA) is on average at least 50% of the systemic exposure after intravenous administration of the same dose-equivalent.
2. The combination of a single oral dose of docetaxel and CsA is well tolerated by the patients.
3. Oral docetaxel without CsA results in a low systemic exposure (<5% of a dose normalized i.v. administration)
4. Weekly oral docetaxel + CsA at a dose equivalent of 30-35mg/m2 i.v. is active in advanced anthracycline pre-treated breast cancer
Ethics approval
The instiutional review board (Protocol Toetsingscommissie [PTC]), Dutch Cancer Institute, Antonie von Leeuwenhoek Hospital (NKI-AVL) approved on 4th of November 1998 (ref: EV98330)
Study design
Randomised controlled proof of concept study
Primary study design
Interventional
Secondary study design
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, advanced breast cancer
Intervention
The study consist of two parts.
1. Part I is Proof of concept study. It consist of two groups of patients:
1.1. Group I is treated in the course 1 with a single oral dose of docetaxel with CsA and 3 weeks later course 2 and all subsequent courses (6 max) consist of a single agent docetaxel i.v., 3 weekly schedule
1.2. Group II is treated in the course 1 with a single oral dose of docetaxel (no CsA) and 3 weeks later course 2 and all subsequent courses (6 max) consist of a single agent docetaxel i.v., 3 weekly schedule
2. Part II Anti-tumour activity is given weekly oral docetaxel with CsA, (q week 8) to patients with measurable disease according to WHO criteria, after 1 prior anthracycline containing pretretment regimen for advanced disease.
Safety Assessments are performed during the baseline, every course/weekly and at the end of the treatment - medical history, physical examination, performance status WHO, Hb, Wbc+diff, platelets, chemistry, chest X-ray, tumour evaluation.
PK analyses are determined on the first 2 occasions of drug administration
Efficacy is estimated during the tumour evaluation (CT, X-rays and US) during the baseline and every second course according to WHO criteria.
In amendment 2 the mass balance part of the study has been added. Three evaluable patients who are enrolled in the part II study were asked to collect their urine and faeces up to 48 hours which will be further analyzed for docetaxel and metabolites using validated analytical assays.
Intervention type
Drug
Phase
Phase I/II
Drug names
Docetaxel, cyclosporin A (CsA)
Primary outcome measure
1. Safety Assessments are performed during the baseline, every course/weekly and at the end of the treatment
1.1. Medical history
1.2. Physical examination
1.3. Performance status WHO
1.4. Haemoglobin (Hb)
1.5. White blood count (WBC) differential platelets
1.6. Chemistry
1.7. Chest X-ray
1.8. Tumour evaluation
2. Pharmakinetic (PK) analyses are determined on the first 2 occasions of drug administration
Secondary outcome measures
1. Efficacy is estimated during the tumour evaluation (CT, X-rays and US) during the baseline and every second course according to WHO criteria.
2. In amendment 2 the mass balance part of the study has been added. Three evaluable patients who are enrolled in the part II study were asked to collect their urine and faeces up to 48 hours which will be further analyzed for docetaxel and metabolites using validated analytical assays.
Overall trial start date
27/10/1998
Overall trial end date
01/06/2001
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients must have:
1. Advanced breast cancer, measurable disease according to WHO criteria
2. Treatment with one anthracycline containing regimen, prior adjuvant chemotherapy is allowed
3. > 18 years
4. Life expectancy >3 months
5. No radiotherapy for at least 4 weeks prior to entry on study
6. WBC > 3.0x10^9/l, platelets > 100x10^9/l
7. WHO performance status 0-2
8. Written informed consent
9. Previous hormonal therapy, immunotherapy, or local radiotherapy (without compromising the indicator lesions is allowed)
10. No history of other neoplasm, except curatively treated nonmelanoma skin cancer and curatively treated carcinoma in situ of the cervix
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
25
Participant exclusion criteria
1. Concomitant use of MDR converting drugs, such as Ca+ - entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol
2. Uncontrolled infectious disease
3. Unresolved (> grade 1) toxicities of previous chemotherapy
4. Impaired renal function (serum creatinine > 160:mol/l, or clearance < 50ml/min)
5. Serum bilirubin > 20:mol/l
6. Serum albumin < 25g/l
7. Bowel obstruction or motility disorders that may influence the reabsorption of drugs
8. Use of H2-receptors antagonist or proton pump inhibitors
9. Childbearing or no adequate contraception
10. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity
11. Symptomatic cerebral or leptomeningeal metastases
12. Unable to give written informed consent
13. Unwilling or unable to undergo blood sampling for pharmacokinetics
14. No prior taxane therapy
Recruitment start date
27/10/1998
Recruitment end date
01/06/2001
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/AVL) (Netherlands)
Sponsor details
Plesmanlaan 121
Amsterdam
1066 CX
Netherlands
j.slijkerman@nki.nl
Sponsor type
Research organisation
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
Basic results (scientific)
Publication list