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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 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: September 19, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial studies radiation therapy to see how well it works 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: whole breast irradiation
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 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 [ 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 [ 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 (standard WBI)
Patients undergo standard WBI over 5-6 weeks.
Radiation: whole breast irradiation
Undergo standard whole breast irradiation
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (WBI, trastuzumab)
Patients receive trastuzumab 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: whole breast irradiation
Undergo standard whole breast irradiation
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the value of trastuzumab given during radiation therapy (RT) compared to RT alone in preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (IIBCR-SCR-DCIS) in women with human epidermal growth factor receptor 2 (HER2)-positive DCIS resected by lumpectomy.

SECONDARY OBJECTIVES:

I. Determine the value of trastuzumab given during RT compared to RT alone in prolonging invasive or DCIS disease-free survival (IDFS)-DCIS.

II. Determine the value of trastuzumab given during RT compared to RT alone in increasing invasive or DCIS recurrence-free interval.

III. Determine the value of trastuzumab given during RT compared to RT alone in improving regional or distant recurrence.

IV. Determine the value of trastuzumab given during RT compared to RT alone in improving the incidence of contralateral invasive or DCIS breast cancer.

V. Determine the value of trastuzumab given during RT compared to RT alone in improving survival.

VI. To explore the effect of trastuzumab on ovarian function.

TERTIARY OBJECTIVES:

I. To determine if the benefit of trastuzumab added to RT will be significantly higher in v-myc avian myelocytomatosis viral oncogene homolog (cMYC)-amplified tumors than in the cMYC non-amplified subset.

II. To determine if the benefit of trastuzumab added to RT will be less in tumors with mutations in the phosphatidylinositol 3 (PI3) kinase gene than in tumors without PI3 kinase gene mutations.

OUTLINE: 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 intravenously (IV) over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I.

After completion of study therapy, patients are followed up 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:

  • The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and for the pre-entry tumor block submission for HER2 testing and B-43 correlative studies
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory)
  • On histologic examination, the tumor must be ductal carcinoma in situ (DCIS) (patients with mixed DCIS and lobular carcinoma in situ [LCIS] are eligible)
  • The DCIS must be HER2-positive as determined by central testing
  • Estrogen and/or progesterone receptor status must be determined prior to randomization (patients with DCIS that is hormone receptor positive or negative are eligible)
  • All DCIS must have been resected by lumpectomy
  • The margins of the resected specimen must be histologically free of DCIS; for patients in whom pathologic examination demonstrates DCIS present at the line of resection, re-excision(s) may be performed to obtain clear margins (patients who require mastectomy are not eligible)
  • If axillary staging is performed, nodal staging must be pN0, pN0(i-), pN0(i+) which is defined as isolated tumor cells =< 0.2 mm, regardless of the method of detection, i.e., immunohistochemistry (IHC) or hematoxylin & eosin (H&E), pN0(mol-), or pN0(mol+); note: axillary staging is not required (refer to American Joint Committee on Cancer [AJCC] Staging Criteria in the Treatment Trial Information section in the Members' Area of the National Surgical Adjuvant Breast and Bowel Project [NSABP] web site for TNM nomenclature and staging information)
  • The interval between the last surgery for excision of DCIS (lumpectomy or re-excision of lumpectomy margins) and randomization must be no more than 120 days

Exclusion Criteria:

  • Invasive (including microinvasion staged as T1mic) breast cancer (patients with DCIS "suspicious" for microinvasion, but not confirmed, are eligible)
  • Nodal staging of pN1 (including pN1mi) (note: axillary staging is 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 (if DCIS is found, the patient is eligible if the DCIS was in the same quadrant of the ipsilateral breast and was resected with clear margins)
  • Contralateral breast cancer (including DCIS)
  • Whole breast irradiation administered before randomization (partial breast irradiation is prohibited)
  • Prior history of breast cancer, including DCIS (patients with a history of LCIS are eligible)
  • Prior anthracycline chemotherapy for any malignancy
  • Cardiac disease that would preclude the use of the drugs included in the B-43 treatment regimens; this includes but is not confined to:

    • Active cardiac disease:

      • Angina pectoris that requires the use of anti-anginal medication;
      • Ventricular arrhythmias except for benign premature ventricular contractions (PVCs) controlled by medication;
      • Conduction abnormality requiring a pacemaker;
      • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
      • 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 (LV) function;
      • Documented congestive heart failure; or
      • Documented cardiomyopathy
  • Uncontrolled hypertension, i.e., systolic blood pressure [BP] greater than 180 mm/Hg and/or diastolic BP greater than 100 mm/Hg (patients with hypertension that is well controlled on medication are eligible)
  • Other nonmalignant systemic disease that would preclude a patient from receiving trastuzumab or radiation therapy or would prevent prolonged follow-up
  • Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence; patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin
  • Pregnancy or lactation at the time of study entry (note: pregnancy testing according to institutional standards should be performed for women of child-bearing potential)
  • Administration of any investigational agent within 30 days before study entry
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769379

  Show 1203 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Melody Cobleigh NRG Oncology Foundation, Inc.
  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, U10CA180868
Study First Received: October 8, 2008
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014