Docetaxel Combined With Ketoconazole in Treatment of Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00212095
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : November 1, 2012
Information provided by (Responsible Party):
Haematology-Oncology, National University Hospital, Singapore

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: docetaxel and ketoconazole Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Docetaxel Combined With Ketoconazole in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor
Study Start Date : June 2005
Actual Primary Completion Date : April 2007
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: docetaxel and ketoconazole Drug: 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.

Primary Outcome Measures :
  1. 1. Evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer. [ Time Frame: 4 months ]
  2. 2. Evaluate the pathological response rate in the primary tumor following four cycles of docetaxel and ketoconazole. [ Time Frame: 5 months ]

Secondary Outcome Measures :
  1. 1. To study tumor genomics and proteomics and serum proteomics in breast cancer in response to docetaxel/ketoconazole. [ Time Frame: 2 years ]
  2. 2. To compare tumor genomics and proteomics and serum proteomics in breast cancer in response to docetaxel/ketoconazole to that induced by docetaxel alone in a prior study (HO B17/02). [ Time Frame: 2 years ]
  3. 3. To correlate docetaxel pharmacokinetics with (1)Genetic polymorphisms of drug metabolizing enzymes(2)Drug toxicity & tumor response(3)Peripheral mononuclear cell gene expression profiles [ Time Frame: 3 years ]
  4. (4) To study ondansetron pharmacokinetics and correlate that with genetic polymorphisms [ Time Frame: 3 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00212095

National University Hospital
Singapore, Singapore
Sponsors and Collaborators
National University Hospital, Singapore
Principal Investigator: Soo-Chin Lee, MD Consultant

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Haematology-Oncology, Senior Consultant, National University Hospital, Singapore Identifier: NCT00212095     History of Changes
Other Study ID Numbers: BR01/07/05
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: November 1, 2012
Last Verified: October 2012

Keywords provided by Haematology-Oncology, National University Hospital, Singapore:
breast cancer
gene expression

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors