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
  Purpose

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.


Condition Intervention Phase
Stage I Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Drug: doxorubicin hydrochloride
Drug: cyclophosphamide
Drug: paclitaxel
Biological: trastuzumab
Drug: tamoxifen citrate
Drug: aromatase inhibition therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 3000
Study Start Date: May 2000
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Drug: tamoxifen citrate
Given orally
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: aromatase inhibition therapy
Given orally
Other Name: inhibition therapy, aromatase
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.
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 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.

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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005970

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Southwest Oncology Group (SWOG) Research Base
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Edith Perez North Central Cancer Treatment Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005970     History of Changes
Other Study ID Numbers: NCI-2012-01849, NCI-2012-01849, ECOG-N9831, CAN-NCIC-MA28, SWOG-N9831, NCCTG-N9831, CALGB-49909, CDR0000067953, GUMC-00224, N9831, N9831, U10CA025224
Study First Received: July 5, 2000
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Trastuzumab
Doxorubicin
Tamoxifen
Paclitaxel
Aromatase Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on April 17, 2014