Radiation Therapy With or Without Trastuzumab in Treating Women With Ductal Carcinoma In Situ Who Have Undergone Lumpectomy

This study is currently recruiting participants.
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00769379
First received: October 8, 2008
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This randomized phase III trial is studying radiation therapy to see how well it works compared with or without trastuzumab in treating women with ductal carcinoma in situ who have undergone lumpectomy. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy is more effective with or without trastuzumab in treating ductal carcinoma in situ.


Condition Intervention Phase
Ductal Breast Carcinoma in Situ
Biological: trastuzumab
Radiation: radiation therapy
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time from randomization to ipsilateral invasive breast cancer, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Time to IIBCR-SCR-DCIS will be compared across treatment arms using cumulative incidence curves, Cox proportional hazard models, and the Kaplan-Meier method.


Secondary Outcome Measures:
  • Invasive or DCIS disease-free survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Events for analysis of IDFS-DCIS include: local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous and basal cell carcinoma of the skin, melanoma in situ, and carcinoma in situ of the colon and cervix), or death from any cause prior to recurrence or second primary cancer. Invasive breast cancer, ipsilateral recurrence, and contralateral breast cancer will be compared across treatment arms using cumulative incidence functions.

  • Invasive or DCIS recurrence-free interval (IRFI-DCIS) [ Time Frame: Time from randomization to first diagnosis of a local, regional or distant recurrence regardless of any intervening contralateral or other second primary cancer, assessed up to 10 years ] [ Designated as safety issue: No ]
    Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.

  • Invasive regional or distant recurrence [ Time Frame: Time from randomization to first diagnosis of regional or distant recurrence, assessed up to 10 years ] [ Designated as safety issue: No ]
    Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.

  • Contralateral breast cancer (invasive or DCIS) [ Time Frame: Time from randomization to first diagnosis of contralateral invasive or DCIS breast cancer, assessed up to 10 years ] [ Designated as safety issue: No ]
    Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.

  • Overall survival (OS) [ Time Frame: Time from randomization to death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.

  • Incidence of post-treatment amenorrhea (absence of menstrual period for at least 12 months) in women who were premenopausal at the time of study entry [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Amenorrhea will be summarized by treatment arm in terms of incidence rates and the ranges, medians, and quantiles of duration.


Estimated Enrollment: 2000
Study Start Date: November 2008
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks.
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II
Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in arm I.
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Radiation: radiation therapy
Undergo standard whole breast irradiation
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the value of radiotherapy with vs without trastuzumab (Herceptin®) in preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS) in women with HER2-positive DCIS resected by lumpectomy.

SECONDARY OBJECTIVES:

I. To determine the value of these regimens in prolonging invasive or DCIS disease-free survival.

II. To determine the value of these regimens in increasing invasive or DCIS recurrence-free interval.

III. To determine the value of these regimens in improving regional or distant recurrence.

IV. To determine the value of these regimens in improving the incidence of contralateral invasive or DCIS breast cancer.

V. To determine the value of these regimens in improving overall survival. VI. To explore the effect of trastuzumab on ovarian function. VII. To determine if the benefit of trastuzumab added to radiotherapy will be significantly higher in cMYC-amplified tumors than in the cMYC nonamplified subset.

VIII. To determine if the benefit of trastuzumab added to radiotherapy will be less in tumors with mutations in the PI3 kinase gene than in tumors without PI3 kinase gene mutations.

OUTLINE: Patients are stratified according to menopausal status (pre- vs post-), plan for hormonal therapy (yes vs no), and nuclear grade (low or intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks.

ARM II: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in arm I.

Tumor tissue samples are analyzed for mRNA and DNA copy numbers of HER2, cMYC, and other candidate predictive genes; PI3K gene mutation status; other candidate predictors of trastuzumab response; and candidate prognostic markers of ductal carcinoma in situ.

After completion of study therapy, patients are followed every 6 months for 5 years and then every 12 months for 5 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed ductal carcinoma in situ (DCIS)

    • Mixed DCIS and lobular carcinoma in situ (LCIS) allowed
  • HER2 receptor-positive as determined by central testing
  • Must have undergone resection by lumpectomy and meets the following criteria:

    • Margins of the resected specimen must be histologically free of DCIS (re-excision to obtain clear margins allowed)
    • No more than 120 days since the last surgery for excision of DCIS (lumpectomy or re-excision of lumpectomy margins)
  • None of the following allowed:

    • Patients who require mastectomy
    • Invasive (including microinvasion staged as T1mic) breast cancer (DCIS "suspicious" for microinvasion, but not confirmed, allowed)
    • Nodal staging of pN1 (including pN1mi) (axillary staging not required)
    • DCIS present in more than one quadrant (multicentric)
    • Masses or clusters of calcification that are clinically or mammographically suspicious unless biopsied and proven to be benign
    • Contralateral breast cancer (including DCIS)
    • History of breast cancer, including DCIS (history of LCIS allowed)
  • Hormone receptor status:

    • Estrogen receptor and/or progesterone receptor-positive or -negative
  • Must submit tumor block for correlative studies
  • Pre- or postmenopausal
  • ECOG performance status 0-1
  • Life expectancy ≥ 10 years (excluding diagnosis of DCIS)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective non-hormonal contraception during and for 6 months after completion of treatment with trastuzumab (Herceptin®)
  • No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
  • No cardiac disease that would preclude the use of study treatment drugs, including, but not limited to, any of the following:

    • Active cardiac disease

      • Angina pectoris that requires the use of anti-anginal medication
      • Ventricular arrhythmias except for benign premature ventricular contractions controlled by medication
      • Conduction abnormality requiring a pacemaker
      • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
      • Clinically significant valvular disease
    • History of cardiac disease

      • Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function
      • Documented congestive heart failure
      • Documented cardiomyopathy
  • No uncontrolled hypertension (i.e., systolic BP > 180 mm Hg and/or diastolic BP > 100 mm Hg) (hypertension that is well controlled on medication allowed)
  • No other nonmalignant systemic disease that would preclude a patient from receiving trastuzumab or radiotherapy or would prevent prolonged follow-up
  • No other malignancies unless patient has been disease-free ≥ 5 years and at low risk for recurrence, except for treated carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, or basal cell or squamous cell carcinoma of the skin
  • No other cancer therapy until the time of first cancer recurrence or second primary cancer
  • No prior whole or partial breast irradiation
  • No prior anthracycline chemotherapy for any malignancy
  • No investigational agents within the past 30 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00769379

  Show 1113 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Melody Cobleigh National Surgical Adjuvant Breast and Bowel Project (NSABP)
  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: NCT00769379     History of Changes
Other Study ID Numbers: NCI-2009-00702, NCI-2009-00702, CDR0000615085, NSABP-B-43, NSABP-B-43, U10CA012027
Study First Received: October 8, 2008
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal, Breast
Carcinoma, Ductal
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014