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Combination Chemotherapy and Trastuzumab in Treating Women With Stage I, Stage II, or Stage III HER2-Positive 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: NCT00629278
Recruitment Status : Unknown
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : March 5, 2008
Last Update Posted : August 7, 2013
Sponsor:
Information provided by:
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 4, 2008
First Posted Date  ICMJE March 5, 2008
Last Update Posted Date August 7, 2013
Study Start Date  ICMJE December 2007
Estimated Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2008)
  • Disease-free survival
  • Overall survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2008)
  • Failure rate at 2 years due to relapse, death, or toxicity
  • Incidence of cardiac events as assessed by NCI CTCAE V3.0
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy and Trastuzumab in Treating Women With Stage I, Stage II, or Stage III HER2-Positive Breast Cancer
Official Title  ICMJE SHORT-HER: MULTICENTRIC RANDOMISED PHASE III TRIAL OF 2 DIFFERENT ADJUVANT CHEMOTHERAPY REGIMENS PLUS 3 VS 12 MONTHS OF TRASTUZUMAB IN HER2 POSITIVE BREAST CANCER PATIENTS
Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known which regimen of combination chemotherapy given together with trastuzumab is most effective in treating breast cancer.

PURPOSE: This randomized phase III trial is comparing two different regimens of combination chemotherapy given together with trastuzumab to see how well they work in treating women with HER2-positive stage I, stage II, or stage III breast cancer.

Detailed Description

OBJECTIVES:

Primary

  • To evaluate if 3 months of trastuzumab (Herceptin®) administered according to the Finnish protocol (9-weekly administrations) is not inferior to 12 months (18 three-weekly administrations) in a standard chemotherapy protocol, in terms of disease-free survival, in patients with HER2-positive early breast cancer.
  • To determine overall survival of patients treated with these regimens.

Secondary

  • To determine the failure rate at 2 years, calculated as cumulative incidence of relapse, contralateral breast cancer (excluding in situ carcinoma), death for all causes, and treatment withdrawal due to toxicity of therapy.
  • To determine the incidence of cardiac events (defined as decrease of ejection fraction (EF) over 15% from basal values, or decrease over 10% with EF absolute value below 50%, or symptomatic cardiac failure, or other cardiac side effects grade 2 or more according to NCI CTCAE v.3.

OUTLINE: This is a multicenter study. Patients are stratified according to nodal status (positive vs negative), hormone-receptor status (estrogen receptor-positive vs progesterone receptor-positive disease), and Regional Coordinating Center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (standard long-term adjuvant treatment-12 months): Patients receive chemotherapy comprising either doxorubicin hydrochloride IV and cyclophosphamide IV or epirubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients then receive paclitaxel IV over 3 hours or docetaxel* IV over 1 hour and concurrent trastuzumab (Herceptin®) IV over 90 minutes. Treatment repeats every 21 days for up to 4 courses.

NOTE: *Patients < 65 years old receive a higher dose of docetaxel and patients ≥ 65 years old receive a lower dose of docetaxel.

After completion of chemotherapy and concurrent trastuzumab, patients receive trastuzumab IV over 30-60 minutes as monotherapy every 21 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.

  • Arm II (experimental short-term adjuvant treatment-3 months): Patients receive docetaxel** IV on day 1. Treatment repeats every 21 days for up to 3 courses. Patients also receive trastuzumab IV over 30-60 minutes on day 1. Treatment repeats weekly for up to 9 weeks (9 doses).

Within 21 days after completion of docetaxel therapy, patients receive fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for up to 3 courses.

NOTE: **Patients < 65 years old receive a higher dose of docetaxel and patients ≥ 65 years old receive a lower dose of docetaxel.

In both arms, patients treated with conservative surgery or those with more than 4 positive axillary nodes undergo radiotherapy within 8 weeks after completion of chemotherapy. Patients enrolled in arm I undergo radiotherapy concurrently with trastuzumab.

Patients with hormone receptor-positive tumor (i.e., estrogen receptor and/or progesterone receptor-positive tumor) also receive hormonal treatment after completion of chemotherapy. Patients enrolled in arm I receive hormonal therapy concurrently with trastuzumab.

Premenopausal patients receive monthly luteinizing-hormone releasing-hormone agonist for 2 years plus daily tamoxifen citrate for 5 years. Post-menopausal patients receive an aromatase inhibitor daily for 5 years.

After completion of study therapy, patients are followed for up to 3 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Biological: trastuzumab
  • Drug: aromatase inhibition therapy
  • Drug: cyclophosphamide
  • Drug: docetaxel
  • Drug: doxorubicin hydrochloride
  • Drug: epirubicin hydrochloride
  • Drug: fluorouracil
  • Drug: paclitaxel
  • Drug: releasing hormone agonist therapy
  • Drug: tamoxifen citrate
  • Procedure: adjuvant therapy
  • Radiation: radiation therapy
Study Arms  ICMJE Not Provided
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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 4, 2008)
2500
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of infiltrating primary breast cancer

    • Stage I-IIIA disease
    • Resected tumor with free margins (i.e., no neoplastic cells on the resected margin)

      • Must have node-negative sentinel node or complete axillary clearance

        • Axillary clearance required for micrometastasis (between 0.2 and 2 mm) in the sentinel node but not for isolated tumor cells
      • Treatment is scheduled to begin within 10 weeks from the date of surgery

        • Date of the last surgery will be taken into account for patients undergoing re-excision of positive margins or axillary lymph node dissection after positive sentinel node biopsy
  • Node positivity or node negativity AND ≥ 1 of the following:

    • T > 2 cm
    • Grade 3
    • Presence of lymphovascular invasion
    • Ki 67 > 20%
    • Age 35 years
    • Hormone receptor negativity (<10%)
  • HER2-positive tumor (3+ by IHC or FISH+ according to the American Society of Clinical Oncology guidelines [i.e., > 2.2; in case of polysomy, with ≥ 6 gene copies])
  • Estrogen receptor-positive and/or progesterone receptor-positive disease

PATIENT CHARACTERISTICS:

  • Female
  • Pre- or postmenopausal status

    • Postmenopausal status defined by ≥ 1 of the following:

      • At least 60 years of age
      • Less than 60 years of age and amenorrheic for ≥ 12 months prior to day 1
      • Less than 60 years of age and amenorrheic for < 12 months prior to day 1 with luteinizing hormone and follicle-stimulating hormone values within postmenopausal range OR without a uterus
      • Prior bilateral oophorectomy
      • Prior radiation castration with amenorrhea for ≥ 6 months
  • ECOG performance status 0-1
  • Suitable for adjuvant chemotherapy
  • WBC > 3,000/mcL
  • ANC > 1,500/mcL
  • Platelet count >100,000/mcL
  • Total bilirubin normal
  • AST and ALT 2.5 times upper limit of normal
  • Creatinine normal
  • Cardiac ejection fraction normal as measured by ECHO or MUGA scan
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy
  • No contraindication to anthracycline, cyclophosphamide, fluorouracil, paclitaxel, or trastuzumab (Herceptin®) treatment
  • No uncontrolled intercurrent illness including, but not limited to, the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • See Patient Characteristics
  • No prior chemotherapy, endocrine therapy, or radiotherapy
  • No other concurrent investigational agents
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 75 Years   (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 Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00629278
Other Study ID Numbers  ICMJE AOUMODENA-SHORT-HER
CDR0000584446 ( Registry Identifier: PDQ (Physician Data Query) )
EUDRACT-2007-004326-25
EU-20825
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Azienda Ospedaliero-Universitaria di Modena
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pier Franco Conte, MD Azienda Ospedaliero-Universitaria di Modena
PRS Account National Cancer Institute (NCI)
Verification Date July 2009

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