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
I. To determine the value of radiotherapy with vs without trastuzumab (Herceptin®) in
preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin
cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS) in women with
HER2-positive DCIS resected by lumpectomy.
I. To determine the value of these regimens in prolonging invasive or DCIS disease-free
II. To determine the value of these regimens in increasing invasive or DCIS recurrence-free
III. To determine the value of these regimens in improving regional or distant recurrence.
IV. To determine the value of these regimens in improving the incidence of contralateral
invasive or DCIS breast cancer.
V. To determine the value of these regimens in improving overall survival. VI. To explore
the effect of trastuzumab on ovarian function. VII. To determine if the benefit of
trastuzumab added to radiotherapy will be significantly higher in cMYC-amplified tumors than
in the cMYC nonamplified subset.
VIII. To determine if the benefit of trastuzumab added to radiotherapy will be less in
tumors with mutations in the PI3 kinase gene than in tumors without PI3 kinase gene
OUTLINE: Patients are stratified according to menopausal status (pre- vs post-), plan for
hormonal therapy (yes vs no), and nuclear grade (low or intermediate vs high). 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 (Herceptin®) IV over 30-90 minutes once in weeks 1 and
4. Patients also undergo WBI as in arm I.
Tumor tissue samples are analyzed for mRNA and DNA copy numbers of HER2, cMYC, and other
candidate predictive genes; PI3K gene mutation status; other candidate predictors of
trastuzumab response; and candidate prognostic markers of ductal carcinoma in situ.
After completion of study therapy, patients are followed every 6 months for 5 years and then
every 12 months for 5 years.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Time from randomization to ipsilateral invasive breast cancer, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS)
Time to IIBCR-SCR-DCIS will be compared across treatment arms using cumulative incidence curves, Cox proportional hazard models, and the Kaplan-Meier method.
Up to 10 years
National Surgical Adjuvant Breast and Bowel Project (NSABP)
United States: Food and Drug Administration
|National Surgical Adjuvant Breast and Bowel Project||Pittsburgh, Pennsylvania 15212-5234|