Docetaxel Combined With Ketoconazole in Treatment of Breast Cancer

NCT ID: NCT00212095

Last Updated: 2012-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2012-06-30

Brief Summary

Patients with locally advanced or metastatic breast cancer and with measurable primary breast tumor will be treated with 70mg docetaxel combined with ketoconazole. Serial tumor biopsies and plasma samples will be taken for gene expression and proteomics studies to identify biomarkers that may predict for treatment response.

Detailed Description

We hypothesize that 70mg docetaxel co-administered with ketoconazole would result in similar clinical efficacy as conventional doses of docetaxel (75mg/m2 body surface area) in terms of clinical and pathological response rates in metastatic breast cancer. We further hypothesize that tumor genomic and proteomic changes and serum proteomic changes would correlate with tumor response. We are also looking to correlate drug pharmacokinetics with treatment toxicity, genotype of drug metabolizing enzymes and transporters, and peripheral mononuclear cell gene expression profiles. The primary objectives are to evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer, and to evaluate the pathological response rate in the primary tumor following four cycles of docetaxel and ketoconazole.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; docetaxel; gene expression; proteomics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

docetaxel and ketoconazole

Group Type: EXPERIMENTAL

docetaxel and ketoconazole

Intervention Type: DRUG

Docetaxel will be obtained locally from the manufacturer. Storage conditions for unopened vials, reconstitution, and storage conditions for the reconstituted solution will follow the manufacturer's recommendations. Docetaxel solutions should be prepared and stored in glass, polypropylene or polyolefin containers. Non-PVC containing and polyethylene-lined administration sets should be used.

Ketoconazole is available commercially in 200 mg tablet. Ketoconazole is to be administered at a dose of 200mg BID orally for six doses, starting two days before docetaxel administration. The fifth dose should be administered on the day of and before administering docetaxel, while the sixth dose should be administered in the evening of the day of docetaxel administration.

Interventions

docetaxel and ketoconazole

Docetaxel will be obtained locally from the manufacturer. Storage conditions for unopened vials, reconstitution, and storage conditions for the reconstituted solution will follow the manufacturer's recommendations. Docetaxel solutions should be prepared and stored in glass, polypropylene or polyolefin containers. Non-PVC containing and polyethylene-lined administration sets should be used.

Ketoconazole is available commercially in 200 mg tablet. Ketoconazole is to be administered at a dose of 200mg BID orally for six doses, starting two days before docetaxel administration. The fifth dose should be administered on the day of and before administering docetaxel, while the sixth dose should be administered in the evening of the day of docetaxel administration.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female, age >= 18 years.
• Histologic or cytologic diagnosis of breast carcinoma.
• T3-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with both diameters 2.0cm or greater as measured by caliper.
• Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer.
• Karnofsky performance status of 70 or higher.
• Estimated life expectancy of at least 12 weeks.
• Adequate organ function including the following:

• Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L Platelets >= 100 x 109/L

• Hepatic: Bilirubin <= 1.5 x upper limit of normal (ULN), ALT or AST <= 2.5x ULN, (or <5 X with liver metastases)

• Renal: creatinine <= 1.5x ULN
• Left ventricular ejection fraction >=50%
• Signed informed consent from patient or legal representative.
• Patients with reproductive potential must use an approved contraceptive method if appropriate (eg, intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

Exclusion Criteria

• Prior treatment for locally advanced or metastatic breast cancer.
• Treatment within the last 30 days with any investigational drug.
• Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Pregnancy.
• Breast feeding.
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Poorly controlled diabetes mellitus.
• Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
• Symptomatic brain metastasis.
• History of significant neurological or mental disorder, including seizures or dementia.
• Peripheral neuropathy of CTC grade 2 or above (NCI CTC version 3).
• History of hypersensitivity to drugs formulated in Tween 80, the vehicle used for commercial docetaxel formulations.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Haematology-Oncology

Senior Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Soo-Chin Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Consultant

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

References

Lim YW, Goh BC, Wang LZ, Tan SH, Chuah BYS, Lim SE, Iau P, Buhari SA, Chan CW, Sukri NB, Cordero MT, Soo R, Lee SC. Pharmacokinetics and pharmacodynamics of docetaxel with or without ketoconazole modulation in chemonaive breast cancer patients. Ann Oncol. 2010 Nov;21(11):2175-2182. doi: 10.1093/annonc/mdq230. Epub 2010 Apr 29.

Reference Type: DERIVED

PMID: 20430905 (View on PubMed)

Other Identifiers

BR01/07/05

Identifier Type: -

Identifier Source: org_study_id