Radiation Therapy With or Without Trastuzumab in Treating Women With Ductal Carcinoma In Situ Who Have Undergone Lumpectomy - Full Text View

Sponsor:	National Surgical Adjuvant Breast and Bowel Project (NSABP)
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00769379

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Breast Cancer	Biological: trastuzumab Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Trastuzumab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Time from randomization to ipsilateral invasive breast cancer, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Invasive or DCIS disease-free survival as assessed by time to local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous cell and b ... [ Designated as safety issue: No ]
Time from randomization to first diagnosis of a local, regional or distant recurrence regardless of any intervening contralateral or other second primary cancer [ Designated as safety issue: No ]
Time from randomization to first diagnosis of regional or distant recurrence [ Designated as safety issue: No ]
Time from randomization to first diagnosis of contralateral invasive or DCIS breast cancer [ Designated as safety issue: No ]
Time from randomization to death from any cause [ Designated as safety issue: No ]
Incidence of post-treatment amenorrhea (absence of menstrual period for at least 12 months) at 18 months in women who were premenopausal at the time of study entry [ Designated as safety issue: No ]
Correlation of cMYC-amplification status with trastuzumab (Herceptin®) in addition to radiotherapy [ Designated as safety issue: No ]
Correlation of PI3 kinase gene mutation status with trastuzumab in addition to radiotherapy [ Designated as safety issue: No ]

Estimated Enrollment:	2000
Study Start Date:	November 2008
Estimated Primary Completion Date:	March 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks.	Radiation: radiation therapy Patients undergo whole breast irradiation
Experimental: 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.	Biological: trastuzumab Given IV Radiation: radiation therapy Patients undergo whole breast irradiation

Detailed Description:

OBJECTIVES:

Primary

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

To determine the value of these regimens in prolonging invasive or DCIS disease-free survival.
To determine the value of these regimens in increasing invasive or DCIS recurrence-free interval.
To determine the value of these regimens in improving regional or distant recurrence.
To determine the value of these regimens in improving the incidence of contralateral invasive or DCIS breast cancer.
To determine the value of these regimens in improving overall survival.
To explore the effect of trastuzumab on ovarian function.
To determine if the benefit of trastuzumab added to radiotherapy will be significantly higher in cMYC-amplified tumors than in the cMYC nonamplified subset.
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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior whole or partial breast irradiation
No prior anthracycline chemotherapy for any malignancy
No investigational agents within the past 30 days
No other cancer therapy until the time of first cancer recurrence or second primary cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769379

Show 769 Study Locations

Sponsors and Collaborators

National Surgical Adjuvant Breast and Bowel Project (NSABP)

National Cancer Institute (NCI)

Investigators

Study Chair:	Melody A. Cobleigh, MD	Rush University Medical Center
Investigator:	Douglas W. Arthur, MD	Massey Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Siziopikou KP, Cobleigh MA, Anderson SJ, et al.: Preliminary results of centralized HER2 testing in DCIS of the breast: NSABP B-43. [Abstract] J Clin Oncol 29 (Suppl 15): A-588, 2011.

Responsible Party:	Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project
ClinicalTrials.gov Identifier:	NCT00769379 History of Changes
Other Study ID Numbers:	CDR0000615085, NSABP-B-43
Study First Received:	October 8, 2008
Last Updated:	February 9, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

ductal breast carcinoma in situ

Additional relevant MeSH terms:

Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal, Breast
Carcinoma, Ductal
Neoplasms by Site
Neoplasms
Breast Diseases

Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012