Primary Chemotherapy With Docetaxel-Capecitabine and Doxorubicin-Cyclophosphamide in Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jo Anne Zujewski, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00005908
First received: June 13, 2000
Last updated: March 13, 2013
Last verified: March 2013
  Purpose

This study will assess the usefulness of a technique called complementary deoxyribonucleic acid (cDNA) microarray-an examination of a wide array of genes to identify disease-associated patterns-for measuring tumor response to chemotherapy in breast cancer patients. The study will look for "markers" that can help select the most effective type of chemotherapy. It will also evaluate the safety and effectiveness of a new drug combination of capecitabine and docetaxel.

Patients age 18 years and older with stage II or III breast cancer whose tumor is 2 centimeters or larger may be eligible for this study. Those enrolled will be treated with surgery, standard chemotherapy using doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), and the capecitabine and docetaxel combination.

Patients will have a physical examination, mammogram and magnetic resonance imaging to evaluate their tumor before beginning treatment. They will then have four 21-day treatment cycles of docetaxel and capecitabine, as follows: docetaxel intravenously (through a vein) on day 1 and capecitabine pills (by mouth) twice a day from days 2 through 15. No drugs will be given from days 16 through 21. This regimen will be repeated four times, after which the tumor will be re-evaluated by physical examination, mammogram, and magnetic resonance imaging.

Patients will then have surgery to remove the cancer-either lumpectomy with removal of the underarm lymph nodes; mastectomy and removal of the underarm lymph nodes; or modified radical mastectomy. After recovery, they will have four more cycles of chemotherapy, this time with a doxorubicin and cyclophosphamide. Both drugs will be given intravenously on day 1 of four 21-day cycles.

Some patients who had a mastectomy (depending on their tumor characteristics and whether tumor cells were found in their lymph nodes) and all those who had a lumpectomy will also have radiation therapy. Patients with hormone receptor-positive tumors will also receive tamoxifen treatment for 5 years.

In addition to the above procedures, all patients will have tumor biopsies (removal of a small piece of tumor tissue) before beginning treatment, on day 1 of cycle 1, before cycle 2, and at the time of surgery, and physical examinations, chest X-rays, bone scans, computerized tomography (CT) scans, electrocardiograms, multi-gated acquisition scan-MUGA (nuclear medicine test of cardiac function) or echocardiograms of heart function, mammograms and blood tests at various times during the study. Patients will be followed at National Institutes of Health (NIH) for 3 years after diagnosis with physical examinations, blood tests, X-rays, and computed tomography (CT) scans.

Although it is not known whether this treatment will help an individual patient's cancer, possible benefits are tumor shrinkage and decreased risk of disease recurrence. In addition, the information gained about genetic changes after chemotherapy will help determine if additional studies on the use of cDNA microarray to measure tumor response are warranted.


Condition Intervention Phase
Breast Cancer
Breast Neoplasm
Drug: Docetaxel - Dose A
Drug: Anastrozole
Drug: cyclophosphamide
Drug: Docetaxel - Dose B
Drug: Doxorubicin hydrochloride
Drug: Tamoxifen Citrate
Drug: Capecitabine - Dose B
Drug: Capecitabine - Dose A
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of Sequential Primary (Neoadjuvant) Combination Chemotherapy With Docetaxel/Capecitabine (TX) and Doxorubicin/Cyclophosphamide (AC) in Primary Breast Cancer With Evaluation of Chemotherapy Effects on Gene Expression

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

  • Overall Clinical Response Rate [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    Overall response rate is defined as the percentage of participants with a CR (complete disappearance of all target lesions), PR (a 30% decrease in the sum of the longest diameter of target lesions) determined by clinical measurements per the Response Evaluation Criteria in Solid Tumors (RECIST) and/or a complete pathologic response (disappearance of all invasive tumor pathologically or presence of ductal carcinoma in situ) per the Chevallier criteria. For details about the RECIST or Chevallier criteria see the protocol link module.

  • Complementary Deoxyribonucleic Acid (cDNA) Expression [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    Patients were classified as responders or non-responders based on change in tumor size by clinical exam and pathologic response.For instance, patients with a pathological complete response, micro-invasive disease at surgery, or clinical complete response after four cycles of treatment were considered responders. Changes in gene expression associated with treatment was assessed before/after chemotherapy. All gene expression summary intensities below 50 were thresholded to the value of 50 and genes showing variability significantly smaller than the median gene variability were screened out.

  • Number of Participants, e.g. Responders and Non-responders With a Percent Change in Expression Patterns After Chemotherapy With Changes in Expression Patterns After Chemotherapy in Preclinical Models [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    Patients were classified as responders or non-responders based on change in tumor size by clinical exam and pathologic response.For instance, patients with a pathological complete response, micro-invasive disease at surgery, or clinical complete response after four cycles of treatment were considered responders. Changes in gene expression associated with treatment was assessed before/after chemotherapy. All gene expression summary intensities below 50 were thresholded to the value of 50 and genes showing variability significantly smaller than the median gene variability were screened out.


Enrollment: 30
Study Start Date: June 2000
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose A-Cohort 1-Arm 1-Docetaxel & Capecitabine
Docetaxel 75 mg/m^2 intravenous day 1, capecitabine 1000 mg/m^2 orally twice daily day 2-15 for 4 cycles
Drug: Docetaxel - Dose A
Dose A-Cohort 1 Docetaxel 75 mg/m^2 intravenous day 1
Other Name: Taxotere/Xeloda
Drug: Anastrozole
1 mg orally daily for five years
Other Name: Arimidex
Drug: cyclophosphamide
600 mg/m^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1
Other Name: Cytoxan
Drug: Doxorubicin hydrochloride
60 mg/m^2 will be administered as a slow intravenous push on day 1
Other Name: Adriamycin
Drug: Tamoxifen Citrate
20 mg/day orally for five years
Other Name: Nolvadex
Drug: Capecitabine - Dose A
capecitabine 1000 mg/m^2 orally twice daily day 2-15 for 4 cycles
Experimental: Dose B-Cohort 2-Arm 2 Reduced dose-Docetaxel & Capecitabine
Docetaxel 60 mg/m^2 intravenous day 1, capecitabine 937.5 mg/m^2 orally twice daily day 2-15 for 4 cycles
Drug: Anastrozole
1 mg orally daily for five years
Other Name: Arimidex
Drug: cyclophosphamide
600 mg/m^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1
Other Name: Cytoxan
Drug: Docetaxel - Dose B
Dose B - Cohort 2 Docetaxel 60 mg/m^2 intravenous day 1
Other Name: Taxotere
Drug: Doxorubicin hydrochloride
60 mg/m^2 will be administered as a slow intravenous push on day 1
Other Name: Adriamycin
Drug: Tamoxifen Citrate
20 mg/day orally for five years
Other Name: Nolvadex
Drug: Capecitabine - Dose B
Dose B - Cohort 2 capecitabine 937.5 mg/m^2 orally twice daily day 2-15

Detailed Description:

This phase II trial in patients with stage II and stage III breast cancer will test the feasibility of using cDNA microarray as a measure of a tumor's biological response to chemotherapeutic agents by characterizing the cDNA expression patterns in breast cancer before and after primary chemotherapy. Thirty-six patients receive docetaxel/capecitabine induction chemotherapy followed by surgery and doxorubicin/cyclophosphamide adjuvant therapy (TX/AC). We will determine the response rate of TX induction therapy and the toxicities of the sequential combinations (TX/AC). We will also obtain tumor tissue for correlative biological determinations.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Stage II or III breast cancer with a tumor size of greater than 2 cm. Patients with a previous biopsy are eligible provided adequate tumor tissue remains for biopsy in this study.

At least 18 years of age.

Adequate hematopoietic function as defined by absolute neutrophil count greater than 1200/mm^3 and platelet count greater than 100,000/mm^3.

Adequate renal function as defined by creatinine less than 1.6 mg/dL.

Adequate hepatic function as defined by total (T.) bilirubin less than 1.4 mg/dL and serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 1.5 times the upper limit of normal and alkaline phosphatase less than 2.5 times upper limit of normal

Zubrod Performance status 0-2.

EXCLUSION CRITERIA:

Medical or psychiatric condition that, in the opinion of the Principal Investigator, would preclude chemotherapy administration. Patients may be evaluated by psychiatry or medical subspecialties as appropriate.

Pregnant or lactating women

Known bleeding disorders

Hypersensitivity to Tween 80 (Polysorbate)

Cardiac ejection fraction below normal limits, myocardial infarction within the past 12 months, or symptomatic arrhythmia requiring medical intervention.

Prior chemotherapy or hormonal therapy for breast cancer. Patients treated with hormonal chemoprevention (tamoxifen or raloxifene) will be eligible.

Active malignancy diagnosed within the last 5 years. (Cervical cancer or non-melanomatous skin cancer that has been treated with curative intent will be eligible).

  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: NCT00005908

Locations
United States, Maryland
National Naval Medical Center
Bethesda, Maryland, United States, 20889
Sponsors and Collaborators
Investigators
Principal Investigator: JoAnne Zujewski, M.D. National Cancer Institute (NCI), National Institutes of Health (NIH)
  More Information

Additional Information:
RECIST  This link exits the ClinicalTrials.gov site

Publications:
Responsible Party: Jo Anne Zujewski, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00005908     History of Changes
Obsolete Identifiers: NCT00020241
Other Study ID Numbers: 000149, 00-C-0149
Study First Received: June 13, 2000
Results First Received: February 14, 2012
Last Updated: March 13, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
cDNA Microarray
Stage II and Stage III Breast Cancer
Biological Response
Molecular Profiling
Fine Needle Aspirate
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Capecitabine
Liposomal doxorubicin
Cyclophosphamide
Fluorouracil
Doxorubicin
Tamoxifen
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014