Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Southwest Oncology Group (SWOG) Research Base
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005970
First received: July 5, 2000
Last updated: April 16, 2014
Last verified: December 2013

July 5, 2000
April 16, 2014
May 2000
May 2020   (final data collection date for primary outcome measure)
Duration of disease-free survival (DFS) [ Time Frame: Time from registration to first adverse event, assessed up to 15 years ] [ Designated as safety issue: No ]
Will be estimated using the Kaplan-Meier method.
Not Provided
Complete list of historical versions of study NCT00005970 on ClinicalTrials.gov Archive Site
Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 15 years ] [ Designated as safety issue: No ]
Will be estimated using the Kaplan-Meier method.
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Overexpressing Node Positive or High-Risk Node Negative Breast Cancer

This randomized phase III trial is studying combination chemotherapy and trastuzumab to see how well they work compared to combination chemotherapy alone in treating women with breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.

PRIMARY OBJECTIVES:

I. Compare the disease-free survival of women with HER-2-overexpressing node-positive or high-risk node-negative breast cancer treated with doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin).

II. Compare the cardiotoxic effects of these regimens in these patients.

SECONDARY OBJECTIVES:

I. Compare the overall survival of patients treated with these regimens.

TERTIARY OBJECTIVES:

I. Determine whether higher levels of shed extracellular domain or autoantibodies to HER-2 and HER-1 measured in the serum prior to treatment are prognostic for disease-free and overall survival in these patients.

II. Determine whether the concordance of HER-2 overexpression is associated with disease-free and overall survival in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (0 vs 1-3 positive nodes by axillary nodal dissection vs 4-9 positive nodes by axillary nodal dissection vs at least 10 positive nodes by axillary nodal dissection vs positive sentinel node with no or negative axillary nodal dissection vs negative sentinel node with no axillary nodal dissection vs node negative by axillary nodal dissection) and receptor status (estrogen receptor [ER] or progesterone receptor [PR] positive vs other). Patients are randomized to 1 of 3 treatment arms.

ARM I*: Patients receive doxorubicin IV and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment.

ARM II*: Patients receive doxorubicin, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab (Herceptin®) IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment.

ARM III: Patients receive doxorubicin and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity.

Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 15 years or until disease progression.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Stage I Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Biological: trastuzumab
    Given IV
    Other Names:
    • anti-c-erB-2
    • Herceptin
    • MOAB HER2
  • Drug: tamoxifen citrate
    Given orally
    Other Names:
    • Nolvadex
    • TAM
    • tamoxifen
    • TMX
  • Drug: aromatase inhibition therapy
    Given orally
    Other Name: inhibition therapy, aromatase
  • Experimental: Arm I
    Patients receive doxorubicin IV and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: paclitaxel
    • Drug: tamoxifen citrate
    • Drug: aromatase inhibition therapy
  • Experimental: Arm II
    Patients receive doxorubicin, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab (Herceptin®) IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: paclitaxel
    • Biological: trastuzumab
    • Drug: tamoxifen citrate
    • Drug: aromatase inhibition therapy
  • Experimental: Arm III

    Patients receive doxorubicin and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity.

    Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.

    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: paclitaxel
    • Biological: trastuzumab
    • Drug: tamoxifen citrate
    • Drug: aromatase inhibition therapy

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
3000
Not Provided
May 2020   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed operable adenocarcinoma of the breast, meeting 1 of the following criteria:

    • Node-positive disease, meeting the following criteria:

      • One or more positive lymph nodes (T1-3, pN1-2, M0)
      • No cN2 disease
      • pN2 disease allowed
      • One positive lymph node by sentinel node biopsy or at least 6 axillary nodes must be examined on axillary node dissection with at least 1 positive lymph node
      • Metaplastic carcinoma allowed
    • High-risk node-negative disease, meeting the following criteria:

      • Node-negative as determined by 1 of the following:

        • Negative sentinel node biopsy
        • No positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection
      • Tumor must be greater than 2.0 cm if estrogen-receptor (ER)- and progesterone-receptor (PR)-positive disease is present OR greater than 1.0 cm if ER and PR negative
  • HER-2 positive

    • Fluorescent in situ hybridization (FISH) must show gene amplification
    • IHC assay must show a strong positive (3+) staining score
    • Ductal carcinoma in situ (DCIS) components must not be counted in determination of the degree of IHC staining or FISH amplification
  • No locally advanced (T4) tumors at diagnosis, including:

    • Tumors fixed to chest wall
    • Peau d'orange
    • Skin ulcerations/nodules
    • Clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
  • No bilateral invasive carcinoma or DCIS (metachronous or synchronous)

    • Unilateral invasive carcinoma and previous metachronous or synchronous DCISof the contralateral breast treated with mastectomy allowed
  • No prior breast cancer except lobular carcinoma in situ (LCIS)
  • No more than 84 days since prior mastectomy or axillary or sentinel node dissection

    • No gross or microscopic disease at margins
  • No significant pericardial effusion
  • Hormone receptor status:

    • ER/PR status known
  • Female
  • Any status
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST no greater than 2 times ULN
  • LVEF normal
  • No prior myocardial infarction or congestive heart failure
  • No prior arrhythmia or cardiovalvular disease that requires medications or is clinically significant
  • No uncontrolled hypertension (diastolic blood pressure [BP] greater than 100 mm Hg and systolic BP greater than 200 mm Hg)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 2 months after study participation
  • No active unresolved infection
  • No known sensitivity to benzyl alcohol
  • No grade 2 or greater neuropathy
  • No other prior malignancy within the past 5 years except:

    • Effectively treated squamous cell or basal cell skin cancer
    • Carcinoma in situ of the cervix treated with surgery only
    • LCIS of the ipsilateral or contralateral breast treated with surgery and/or tamoxifen only
  • No prior biologic therapy or immunotherapy for breast cancer
  • No prior chemotherapy for breast cancer
  • No prior anthracycline or taxane
  • Prior tamoxifen or any other hormonal therapy for breast cancer allowed if administered for no more than 4 weeks
  • Prior tamoxifen or raloxifene for chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (e.g., prior LCIS) allowed
  • No concurrent tamoxifen or raloxifene
  • No concurrent hormonal therapy (e.g., birth control pills or hormone replacement therapy)
  • No prior radiotherapy for breast cancer
  • See Disease Characteristics
  • No concurrent digitalis or beta-blockers for congestive heart failure
  • No concurrent medications for cardiac arrhythmias or angina pectoris
  • No concurrent cardioprotective drugs
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00005970
NCI-2012-01849, NCI-2012-01849, ECOG-N9831, CAN-NCIC-MA28, SWOG-N9831, NCCTG-N9831, CALGB-49909, CDR0000067953, GUMC-00224, N9831, N9831, U10CA025224
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
  • Southwest Oncology Group (SWOG) Research Base
  • Cancer and Leukemia Group B
  • NCIC Clinical Trials Group
  • Eastern Cooperative Oncology Group
Principal Investigator: Edith Perez North Central Cancer Treatment Group
National Cancer Institute (NCI)
December 2013

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