Condition category
Cancer
Date applied
25/08/2010
Date assigned
10/11/2010
Last edited
10/11/2010
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

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 measures

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes