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Combination Chemotherapy in Treating Patients With 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.
 
ClinicalTrials.gov Identifier: NCT00003088
Recruitment Status : Completed
First Posted : September 6, 2004
Last Update Posted : April 29, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE September 6, 2004
Last Update Posted Date April 29, 2020
Study Start Date  ICMJE September 1997
Actual Primary Completion Date April 2003   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2011)
Disease free survival [ Time Frame: 4 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy in Treating Patients With Breast Cancer
Official Title  ICMJE A Randomized Phase III Trial of Sequential Chemotherapy Using Doxorubicin, Paclitaxel, and Cyclophosphamide or Concurrent Doxorubicin and Cyclophosphamide Followed by Paclitaxel at 14 or 21 Day Intervals in Women With Node Positive Stage II/IIIA Breast Cancer
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs at different times or combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy consisting of either doxorubicin, cyclophosphamide, or paclitaxel given at different times with that of combination chemotherapy consisting of doxorubicin plus cyclophosphamide followed by paclitaxel in treating women with stage II or stage IIIA breast cancer.

Detailed Description

OBJECTIVES: I. Compare the sequential chemotherapy with doxorubicin, paclitaxel and cyclophosphamide to combined doxorubicin and cyclophosphamide followed by paclitaxel for disease free and overall survival in women with node positive stage II or IIIA breast cancer. II. Determine whether increasing the dose density of adjuvant chemotherapy will improve disease free and overall survival. III. Compare the toxicity in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized into one of four arms (sequential chemotherapy every 2 weeks vs every 3 weeks vs concurrent chemotherapy followed by paclitaxel every 2 weeks vs every 3 weeks). All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy plus axillary node dissection. Adjuvant chemotherapy is started within 84 days following the last surgical procedure. Arm I: Patients receive sequential chemotherapy every 3 weeks. Doxorubicin IV is administered once every 3 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 3 weeks for 4 doses. Cyclophosphamide IV is administered once every 3 weeks for 4 doses following paclitaxel. Arm II: Patients receive sequential chemotherapy every 2 weeks. Doxorubicin IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 2 weeks for 4 doses. Cyclophosphamide IV is administered once every 2 weeks for 4 doses following paclitaxel. Filgrastim (G-CSF) is administered by subcutaneous injection on days 3-10 after each dose of doxorubicin, paclitaxel, and cyclophosphamide. Arm III: Patients receive combination chemotherapy every 3 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 3 weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 3 weeks for 4 doses following combination chemotherapy. Arm IV: Patients receive combination chemotherapy every 2 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 2 weeks for 4 doses following combination chemotherapy. G-CSF is administered by subcutaneous injection on days 3-10 after each dose of doxorubicin/cyclophophamide and after each dose of paclitaxel. After completion of all chemotherapy, patients receive tamoxifen orally for 5 years. Patients undergo radiotherapy 4-6 weeks after the completion of chemotherapy. Patients are followed every 6 months for 5 years, then annually until death.

PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study within 22 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: cyclophosphamide
    given IV
  • Drug: doxorubicin hydrochloride
    given IV
  • Drug: paclitaxel
    given IV
Study Arms  ICMJE
  • Experimental: Sequential chemotherapy 21 days
    Patients received doxorubicin 60 mg/m^2 every 3 weeks for four cycles followed by paclitaxel 175 mg/m^2 every 3 weeks for four cycles followed by cyclophosphamide 600 mg/m^2 every 3 weeks for four cycles.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: paclitaxel
  • Experimental: Concurrent chemotherapy 14 days
    Patients received doxorubicin 60 mg/m^2 plus cyclophosphamide 600 mg/m^2 every 2 weeks for four cycles followed by paclitaxel 175 mg/m^2 every 2 weeks for four cycles with filgrastim days 3 to 10 of each cycle at 5 µg/kg rounded to either 300 or 480 µg total dose.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: paclitaxel
  • Experimental: Sequential chemotherapy 14 days
    Patients received doxorubicin 60 mg/m2 every 2 weeks for four cycles followed by paclitaxel 175 mg/m2 every 2 weeks for four cycles followed by cyclophosphamide 600 mg/m2 every 2 weeks for four cycles, with filgrastim days 3 to 10 of each cycle (a total of seven doses) at 5 µg/kg, which could be rounded to either 300 or 480 µg total dose.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: paclitaxel
  • Experimental: Concurrent chemotherapy 21 days
    Patients received doxorubicin 60 mg/m^2 plus cyclophosphamide 600 mg/m^2 every 3 weeks for four cycles followed by paclitaxel 175 mg/m^2 every 3 weeks for four cycles.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2011)
2005
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2003
Actual Primary Completion Date April 2003   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  1. Required Tumor Parameters

    1.1 Patients with operable, histologically confirmed adenocarcinoma of the female breast and positive lymph nodes. Node positivity may be determined by either an axillary node dissection or a positive sentinel node finding by immunohistochemistry or histology. This includes any patient with one or more positive lymph nodes whose tumors are T0, T1, 2 or 3 and N1, N2, MO. Patients with metaplastic carcinoma are eligible. Bilateral disease does not exclude patients from entry.

    1.2 Tumors that are locally advanced at diagnosis are not eligible. This is left to investigator judgment. Patients with tumors fixed to the chest wall, peau d'orange skin changes, skin ulcerations, or clinical inflammatory changes (T4 disease) are excluded from this study. Dermal lymphatic involvement noted on pathology without clinical inflammatory changes will not exclude a patient from this study.

    1.3 Patients with any ERP/PgR status are eligible.

  2. Prior treatment:

    2.1 <84 days from mastectomy or within 84 days of axillary dissection if the patient's most extensive breast surgery was a breast sparing procedure.

    2.2 Surgical resection margins - All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy. Node dissection: patients may have had either an axillary node dissection or sentinel lymph node biopsy before beginning treatment on protocol.

    • Mastectomy: There should be no evidence of gross or microscopic tumor at the surgical resection margins noted in the final surgery or pathology reports for patients who have had a modified radical mastectomy. Patients with close margins (tumor < 1 mm from margin) are eligible.
    • Segmental mastectomy (lumpectomy): Although clear margins are preferable, DCIS or LCIS at the surgical resection margin will not render a patient who has undergone a segmental mastectomy ineligible for this study. Invasive tumor at the final resection margin will render a patient ineligible.

    2.3 No prior chemotherapy.

    2.4 No prior radiation therapy for this malignancy. Patients who received radiation to the breast for DCIS are eligible. Patients who have had segmental mastectomy will be treated with radiotherapy according to standard procedures in the treating physician's institution after completion of all chemotherapy. Patients who have had modified radical mastectomy may also receive radiotherapy at the discretion of the treating physician according to institutional guidelines.

    2.5 Patients may receive up to four weeks of tamoxifen therapy for this malignancy and still be eligible for study entry. Patients who received tamoxifen for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer) are eligible. Tamoxifen therapy should be discontinued before the patient is enrolled on this study.

  3. Age > 18. There is no upper age limit for enrollment on this study.
  4. Required initial laboratory data:

    • Granulocyte count > 1000/mm3
    • Platelet count > 100,000/mm3
    • Bilirubin within upper limits of normal
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00003088
Other Study ID Numbers  ICMJE CALGB-9741
U10CA031946 ( U.S. NIH Grant/Contract )
CALGB-9741
CDR0000065788 ( Registry Identifier: NCI Physician Data Query )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Marc L. Citron, MD ProHEALTH Care Associates, LLP
PRS Account Alliance for Clinical Trials in Oncology
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP