Clinical Trials /

Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer

NCT00712140

Description:

RATIONALE: 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 trastuzumab is more effective in treating early breast cancer. PURPOSE: This randomized phase III trial is comparing two trastuzumab regimens to see how well they work in treating women with HER2-positive early breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer
  • Official Title: Persephone: Duration of Trastuzumab With Chemotherapy in Women With Early Stage Breast Cancer: Six Months Versus Twelve

Clinical Trial IDs

  • ORG STUDY ID: CDR0000598391
  • SECONDARY ID: WMS-PERSEPHONE
  • SECONDARY ID: MREC-PERSEPHONE
  • SECONDARY ID: EUDRACT: 2006-007018-39
  • SECONDARY ID: ISRCTN 52968807
  • SECONDARY ID: MREC 07/MRE08/35
  • SECONDARY ID: EU-20858
  • SECONDARY ID: CRUK-BRD/07/137
  • NCT ID: NCT00712140

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
trastuzumabArm I
parenteral chemotherapyArm I

Purpose

RATIONALE: 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 trastuzumab is more effective in treating early breast cancer. PURPOSE: This randomized phase III trial is comparing two trastuzumab regimens to see how well they work in treating women with HER2-positive early breast cancer.

Detailed Description

      OBJECTIVES:

      Primary

        -  Determine disease-free survival of women with HER2-positive early breast cancer treated
           with neoadjuvant or adjuvant trastuzumab (Herceptin®) for 6 months versus 12 months.

      Secondary

        -  Determine the overall survival of patients treated with these regimens.

        -  Determine the expected incremental cost effectiveness (cost per quality adjusted life
           year gained) for 6 months versus 12 months trastuzumab.

        -  Determine cardiac function as assessed by left ventricular ejection fraction every 3
           months during treatment.

        -  Analyze the predictive factors for development of cardiac damage.

      OUTLINE: This is a multicenter study. Patients are stratified according to estrogen receptor
      status (negative vs positive); chemotherapy timing (adjuvant vs neoadjuvant); chemotherapy
      type (anthracycline based [no taxane] vs taxane and anthracyclines vs taxane-based [no
      anthracyclines]); and trastuzumab (Herceptin®) timing (concurrently vs sequentially [with
      respect to chemotherapy]). Patients are randomized to 1 of 2 treatment arms.

        -  Arm I: Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats
           every 3 weeks for up to 12 months in the absence of disease progression or unacceptable
           toxicity.

        -  Arm II: Patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats
           every 3 weeks for up to 6 months in the absence of disease progression or unacceptable
           toxicity.

      All patients also receive standard chemotherapy regimens as per local institutional protocols
      either concurrently with or sequentially to trastuzumab.

      Patients complete quality of life questionnaires using the EuroQoL-5D (EQ-5D) at baseline and
      periodically during study treatment. Patients also complete a diary on out-of-pocket expenses
      associated with their condition (i.e., travel expenses, over-the-counter medicines and
      supplements, complementary therapies not funded by NHS, home help, and time away from work)
      for cost-effective analysis.

      After completion of study therapy, patients are followed every 3 months for 1 year, then
      every 6 months for 1 year, and annually thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm IActive ComparatorPatients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab.
  • parenteral chemotherapy
Arm IIExperimentalPatients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. All patients also receive standard chemotherapy regimens as per local institutional protocols either concurrently with or sequentially to trastuzumab.
  • parenteral chemotherapy

Eligibility Criteria

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed invasive breast cancer

          -  No evidence of metastatic disease

          -  Overexpression of HER2 receptor defined as 3+ or 2+ HER2 positivity measured by
             fluorescent in situ hybridization (FISH) gene amplification

          -  Indication for chemotherapy based on the following clinical and histopathological
             features:

               -  Receiving or scheduled to receive neoadjuvant chemotherapy

                    -  Time between diagnosis biopsy and start date of chemotherapy should be less
                       than 1 month

               -  Receiving or scheduled to receive adjuvant chemotherapy

                    -  Completely resected disease, with negative surgical margins (apart from deep
                       margin if full thickness resection)

                    -  Marginally resected disease and/or positive sentinel nodes allowed provided
                       patients undergo completion of surgery (breast and/or axillary clearance)
                       after chemotherapy

          -  Hormone receptor status known

        PATIENT CHARACTERISTICS:

          -  Menopausal status not specified

          -  ECOG performance status 0-1

          -  Adequate bone marrow, hepatic, and renal function

          -  LVEF normal by ECHO or MUGA

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

          -  No clinically significant cardiac abnormalities

          -  No myocardial infarction within the past 6 months

          -  No uncontrolled or malignant hypertension

          -  No history of atrioventricular arrhythmia and/or congestive heart failure (even under
             medical control), or active second or third degree cardiac block

          -  No history of allergy to drugs containing polysorbate 20 and the excipient polysorbate
             80 (TWEEN 80®) or history of allergy to mouse proteins

          -  No co-morbidity significantly adding to risks associated with cytotoxic chemotherapy
             (i.e., severe chronic obstructive pulmonary disease or poorly controlled diabetes)

          -  No prior diagnosis of malignancy unless managed by surgical treatment only and
             disease-free for 10 years

               -  Prior basal cell carcinoma, cervical carcinoma in situ, or ductal carcinoma in
                  situ of the breast allowed if treated by surgery only

          -  No concomitant medical or psychiatric problems that might preclude completion of
             treatment or follow-up

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior chemotherapy or radiotherapy

          -  Concurrent radiotherapy allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free survival
Time Frame:
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival
Time Frame:
Safety Issue:
Description:
Measure:Cost effectiveness and quality of life
Time Frame:
Safety Issue:
Description:
Measure:Cardiac function and analysis of predictive factors for development of cardiac damage
Time Frame:
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Warwick Medical School

Trial Keywords

  • stage IA breast cancer
  • stage IB breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • HER2-positive breast cancer

Last Updated

September 1, 2011