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Oral bioavailability of docetaxel in combination with cyclosporin A and activity of the combination in advance breast cancer

Completed
Conditions
Cancer, advanced breast cancer
Cancer
Malignant neoplasm of breast
Registration Number
ISRCTN90476883
Lead Sponsor
The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI/AVL) (Netherlands)
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Female
Target Recruitment
25
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

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

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
1. Safety Assessments are performed during the baseline, every course/weekly and at the end of the treatment <br>1.1. Medical history<br>1.2. Physical examination<br>1.3. Performance status WHO<br>1.4. Haemoglobin (Hb)<br>1.5. White blood count (WBC) differential platelets<br>1.6. Chemistry<br>1.7. Chest X-ray<br>1.8. Tumour evaluation<br>2. Pharmakinetic (PK) analyses are determined on the first 2 occasions of drug administration
Secondary Outcome Measures
NameTimeMethod
1. Efficacy is estimated during the tumour evaluation (CT, X-rays and US) during the baseline and every second course according to WHO criteria.<br>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.
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