Serum Proteomics to Predict Gemcitabine Sensitivity in Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00212069
First received: September 13, 2005
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

Tumors are heterogeneous with varying response to chemotherapeutic agents. We hypothesize that tumors that are sensitive to a particular chemotherapeutic agent have a distinctive tumor protein profile compared to those that are resistant. We further hypothesize that since tumor is continuously perfused by serum, serum protein profile can be used as a surrogate marker of tumor protein profile. The primary objective of this study is to identify a serum protein profile that predicts gemcitabine/carboplatin sensitivity or resistance in breast cancer patients with prior exposure to anthracyclines and taxanes. Secondary objectives are to establish the serum protein profile of breast cancer patients who have had prior exposure to anthracyclines and taxanes, and to study the pharmacogenetics of gemcitabine toxicity by correlating germline genotype of transporters and drug metabolizing enzymes with plasma and intracellular gemcitabine pharmacokinetics.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: gemcitabine, carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Serum Protein Profiling as a Predictor of Gemcitabine Sensitivity in Breast Cancer With Prior Exposure to Anthracyclines and Taxanes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To identify a serum protein profile that predicts gemcitabine/carboplatin sensitivity or resistance in breast cancer patients with prior exposure to anthracyclines and taxanes.

Secondary Outcome Measures:
  • a. To establish the serum protein profile of breast cancer patients who have had prior exposure to anthracyclines and taxanes.
  • b. To study the pharmacogenetics of gemcitabine toxicity by correlating germline genotype of transporters and drug metabolizing enzymes with plasma and intracellular gemcitabine pharmacokinetics.

Estimated Enrollment: 30
Study Start Date: March 2004
Study Completion Date: April 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Detailed Description:

Metastatic breast cancer patients previously treated with anthracyclines and taxanes will be treated with gemcitabine and carboplatin every 3 weeks. Serial plasma samples will be collected for proteomics profiling with SELDI-MS that will be correlated with tumor response to identify biomarkers that may predict for chemotherapy sensitivity.

  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.
  • Stage IV breast cancer with prior exposure to anthracyclines and taxanes, either in the neoadjuvant, adjuvant or metastatic setting.
  • Presence of at least one uni-dimensionally measurable, non-CNS indicator lesion defined by radiologic study or physical examination
  • For patients with previous radiotherapy, the indicator lesion(s) must not be within the previous radiation field. The last dose of radiotherapy should be at least 3 weeks prior to study entry. The total radiotherapy received should not be more than 30% of the bone marrow.
  • Karnofsky performance status of 70 or higher.
  • Estimated life expectancy of at least 12 weeks.
  • Adequate organ function including the following:

    - Bone marrow: White blood cells (WBC) >= 3.5 x 109/L Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L Platelets >= 100 x 109/L Haemoglobin >= 9g/dL

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

    - Renal: Creatinine clearance >30ml/minute, based on the Cockcroft formula

  • 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:

  • 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.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
  • Symptomatic brain metastasis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00212069

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

ClinicalTrials.gov Identifier: NCT00212069     History of Changes
Other Study ID Numbers: BR01/12/03
Study First Received: September 13, 2005
Last Updated: December 10, 2013
Health Authority: Singapore: Health Sciences Authority

Keywords provided by National University Hospital, Singapore:
breast cancer
serum proteomics
gemcitabine
carboplatin
chemotherapy sensitivity

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 01, 2014