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 (NSABP B-43)
B-43 will determine if invasive or DCIS disease-free survival, recurrence-free interval, and overall survival can be improved with the addition of trastuzumab to RT. The effects of trastuzumab on ovarian function in premenopausal
women will also be assessed.
Submission of a representative tumor block to Rush University Medical Center (RUMC) for HER2 testing is required prior to randomization. If the DCIS is found to be HER2-positive and the patient is enrolled in B-43, the block will also be used for B-43 correlative studies. Patients whose DCIS is determined to be HER2-negative by testing at RUMC will not be eligible for participation in B-43.
Eligible patients will be randomized to receive either RT alone or two doses of trastuzumab given concurrently with RT. The RT must be whole breast irradiation (with or without a boost) delivered over 5-6 weeks or, at the investigator and amp;apos;s discretion, accelerated fractionation may be used.
For patients with DCIS that is hormone receptor-positive, hormonal therapy should be given for a minimum of 5 years.
The sample size for B-43 will be 2000 patients to be accrued over a period of 7.93 years.
The patient must have consented to participate and must have signed and dated
an appropriate 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 (see Section 6.1).
-- Patients must be female.
--Patients must be 18 years of age or older.
-- Patients must have an 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 (see Sections 6.1 and 6.2 for details). NSABP B-43 - Page 16
--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.)
--10 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., IHC or H&E, pN0(mol–), or pN0(mol+). Note: Axillary staging is not required. (Refer to AJCC Staging Criteria in the Treatment Trial Information section in the Members' Area of the NSABP Web site for TNM nomenclature and staging information.)
-- The interval between the last surgery for excision of DCIS (lumpectomy or reexcision of lumpectomy margins) and randomization must be no more than 120 days.
-- Conditions for patient ineligibility