Overview

This trial is active, not recruiting.

Conditions ductal breast carcinoma in situ, her2/neu positive
Treatments laboratory biomarker analysis, trastuzumab, whole breast irradiation
Phase phase 3
Target HER2
Sponsor National Cancer Institute (NCI)
Start date November 2008
End date March 2019
Trial size 2000 participants
Trial identifier NCT00769379, B-43, CDR0000615085, NCI-2009-00702, NSABP-B-43, U10CA012027, U10CA180868

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients undergo standard WBI over 5-6 weeks.
laboratory biomarker analysis
Correlative studies
whole breast irradiation
Undergo standard whole breast irradiation
(Experimental)
Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I.
laboratory biomarker analysis
Correlative studies
trastuzumab ABP 980
Given IV
whole breast irradiation
Undergo standard whole breast irradiation

Primary Outcomes

Measure
Time from randomization to ipsilateral invasive breast cancer, ipsilateral skin cancer recurrence, or ipsilateral DCIS
time frame: Up to 10 years

Secondary Outcomes

Measure
Contralateral breast cancer (invasive or DCIS)
time frame: Time from randomization to first diagnosis of contralateral invasive or DCIS breast cancer, assessed up to 10 years
Incidence of post-treatment amenorrhea (absence of menstrual period for at least 12 months) in women who were premenopausal at the time of study entry
time frame: 18 months
Invasive or DCIS disease-free survival
time frame: Up to 10 years
Invasive or DCIS recurrence-free interval
time frame: Time from randomization to first diagnosis of a local, regional or distant recurrence regardless of any intervening contralateral or other second primary cancer, assessed up to 10 years
Invasive regional or distant recurrence
time frame: Time from randomization to first diagnosis of regional or distant recurrence, assessed up to 10 years
Overall survival
time frame: Time from randomization to death from any cause, assessed up to 10 years

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

Official title 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
Principal investigator Melody Cobleigh
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).