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)

Summary

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'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.

Participant Eligibility

Patient Selection Guidelines:

* Pre-entry central HER2 testing is required for all patients. The correlative studies are required for all patients enrolled in B-43. Therefore, submission of a representative tumor block for the B-43 trial is required. Submission of alternative tissue samples is NOT permitted. The local pathology department policy regarding release of blocks must be considered when screening patients.

* The best representative sample for HER2 central testing may be obtained from the lumpectomy specimen or from the core biopsy specimen. However, the pre-entry central HER2 testing consent form must be signed and dated by the patient after her lumpectomy but before submission of the representative tumor block.
Patients with a life expectancy of less than 10 years, excluding the diagnosis of ductal carcinoma in situ of the breast. (Comorbid conditions should be taken into consideration, but not the DCIS diagnosis.)

* Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy and for at least 6 months after completion of trastuzumab.

A patient cannot be considered eligible for this study unless all of the following conditions are met:

--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.
--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.)
--Menopausal status must be determined prior to randomization. An FSH level may be required.
-- 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(ix), 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(molx), 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.