Radiation Therapy With or Without Trastuzumab in Treating Women With Ductal Carcinoma In Situ Who Have Undergone Lumpectomy
Condition: Breast Ductal Carcinoma In Situ
MeSH terms: Carcinoma; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Ductal, Breast
Intervention: Laboratory Biomarker Analysis; Trastuzumab; Whole Breast Irradiation
Intervention description: Correlative studies; Given IV; Undergo standard whole breast irradiation
Intervention MeSH terms: Trastuzumab; Trastuzumab biosimilar HLX02
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2014.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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

          -  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