Radiation Therapy With or Without Trastuzumab in Treating Women With Ductal Carcinoma In Situ Who Have Undergone Lumpectomy
Radiation Therapy With or Without Trastuzumab in Treating Women With Ductal Carcinoma In Situ Who Have Undergone Lumpectomy
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.
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 treatment, patients are followed up every 6 months for 5 years and
 then every 12 months for 5 years.
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

 -  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