Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase III trial is studying radiation therapy to see how well it works compared 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.

Further Study Information

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

I. To determine the value of these regimens in prolonging invasive or DCIS disease-free survival.

II. To determine the value of these regimens in increasing invasive or DCIS recurrence-free interval.

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 mutations.

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.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed ductal carcinoma in situ (DCIS)

• Mixed DCIS and lobular carcinoma in situ (LCIS) allowed

• HER2 receptor-positive as determined by central testing

• Must have undergone resection by lumpectomy and meets the following criteria:

• Margins of the resected specimen must be histologically free of DCIS (re-excision to obtain clear margins allowed)

• No more than 120 days since the last surgery for excision of DCIS (lumpectomy or re-excision of lumpectomy margins)

• None of the following allowed:

• Patients who require mastectomy

• Invasive (including microinvasion staged as T1mic) breast cancer (DCIS "suspicious" for microinvasion, but not confirmed, allowed)

• Nodal staging of pN1 (including pN1mi) (axillary staging 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

• Contralateral breast cancer (including DCIS)

• History of breast cancer, including DCIS (history of LCIS allowed)

• Hormone receptor status:

• Estrogen receptor and/or progesterone receptor-positive or -negative

• Must submit tumor block for correlative studies

• Pre- or postmenopausal

• ECOG performance status 0-1

• Life expectancy ≥ 10 years (excluding diagnosis of DCIS)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective non-hormonal contraception during and for 6 months after completion of treatment with trastuzumab (Herceptin®)

• No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements

• No cardiac disease that would preclude the use of study treatment drugs, including, but not limited to, any of the following:

• Active cardiac disease

• Angina pectoris that requires the use of anti-anginal medication

• Ventricular arrhythmias except for benign premature ventricular contractions controlled by medication

• Conduction abnormality requiring a pacemaker

• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication

• 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 function

• Documented congestive heart failure

• Documented cardiomyopathy

• No uncontrolled hypertension (i.e., systolic BP > 180 mm Hg and/or diastolic BP > 100 mm Hg) (hypertension that is well controlled on medication allowed)

• No other nonmalignant systemic disease that would preclude a patient from receiving trastuzumab or radiotherapy or would prevent prolonged follow-up

• No other malignancies unless patient has been disease-free ≥ 5 years and at low risk for recurrence, except for treated carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, or basal cell or squamous cell carcinoma of the skin

• No other cancer therapy until the time of first cancer recurrence or second primary cancer

• No prior whole or partial breast irradiation

• No prior anthracycline chemotherapy for any malignancy

• No investigational agents within the past 30 days

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Melody Cobleigh

Principal Investigator

U.S.A.
Pennsylvania
	Pittsburgh
	National Surgical Adjuvant Breast and Bowel Project
		Melody A. Cobleigh	Ph: 312-942-5498
			Email: clinical_trials@rush.edu
		Melody A. Cobleigh	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00769379
Information obtained from ClinicalTrials.gov on March 26, 2013

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