Oral bioavailability of docetaxel in combination with cyclosporin A and activity of the combination in advance breast cancer
| ISRCTN | ISRCTN90476883 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN90476883 |
| Secondary identifying numbers | N98ODO |
- Submission date
- 25/08/2010
- Registration date
- 10/11/2010
- Last edited
- 10/11/2010
- 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 | Randomised controlled proof of concept study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | 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 | Oral bioavailability of docetaxel in combination with cyclosporin A and activity of the combination in advance breast cancer: A randomised controlled trial |
| Study acronym | N98ODO |
| Study objectives | 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(s) | The instiutional review board (Protocol Toetsingscommissie [PTC]), Dutch Cancer Institute, Antonie von Leeuwenhoek Hospital (NKI-AVL) approved on 4th of November 1998 (ref: EV98330) |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 27/10/1998 |
| Completion date | 01/06/2001 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 25 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 27/10/1998 |
| Date of final enrolment | 01/06/2001 |
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/AVL) (Netherlands)
Research organisation
Research organisation
Plesmanlaan 121
Amsterdam
1066 CX
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 |
