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Docetaxel Combined With Ketoconazole in Treatment of Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Haematology-Oncology, National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00212095
First received: September 13, 2005
Last updated: October 31, 2012
Last verified: October 2012
History of Changes
  Purpose

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 Intervention Phase
Metastatic Breast Cancer
 Drug: docetaxel and ketoconazole
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • 1. Evaluate the clinical response rate of 70mg docetaxel with ketoconazole in metastatic breast cancer. [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  • 2. Evaluate the pathological response rate in the primary tumor following four cycles of docetaxel and ketoconazole. [ Time Frame: 5 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1. To study tumor genomics and proteomics and serum proteomics in breast cancer in response to docetaxel/ketoconazole. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • (4) To study ondansetron pharmacokinetics and correlate that with genetic polymorphisms [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: June 2005
Study Completion Date: June 2012
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00212095

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

No publications provided by National University Hospital, Singapore

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Haematology-Oncology, Senior Consultant, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT00212095     History of Changes
Other Study ID Numbers: BR01/07/05
Study First Received: September 13, 2005
Last Updated: October 31, 2012
Health Authority: Singapore: Health Sciences Authority

Keywords provided by National University Hospital, Singapore:
breast cancer
docetaxel
gene expression
proteomics

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ketoconazole
Docetaxel
14-alpha Demethylase Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 17, 2013