Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

Diagnostic Procedures in Women With Locally Advanced Breast Cancer Who Are Receiving Chemotherapy Before Breast Cancer Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Diagnostic	Active	18 and over	NCI	CALGB-150007 NCT00033397

Objectives

Primary

1. Support accrual to the ACRIN-6657/CALGB-150012 magnetic resonance imaging (MRI) correlative science study.
2. Determine whether molecular markers, alone or in combination with MRI, at the time of diagnosis or early in the course of therapy, predict 3-year disease-free survival (DFS) in women with locally advanced breast cancer who are receiving neoadjuvant chemotherapy.
3. Identify two groups of participants who have statistically different 3-year DFS, based on 1 or more biomarkers, including MRI.
4. Determine whether biomarkers, in combination with MRI, early in the course of chemotherapy, improve the prediction of 3-year DFS and are at least as good of a predictor of DFS as residual disease at the time of surgery in these patients.
5. Determine whether molecular markers are associated with specific imaging patterns seen on MRI of these patients.
6. Predict response with MRI results and marker data from cell cycle check points, proliferation, angiogenesis, hormone receptors, and molecular profiles in these patients.

Secondary

1. Determine the molecular predictors of lack of radiologic complete response (CR) in HER-2/neu negative patients (immunohistochemistry [IHC] score of 0, 1+, 2 and fluorescence in situ hybridization [FISH] not amplified) after a neoadjuvant anthracycline-based regimen.
2. Determine the molecular predictors of lack of radiologic CR in HER-2/neu positive patients (IHC 3+ or FISH amplified > 2.0) after a neoadjuvant anthracycline-based regime followed by a taxane alone regimen or in combination with trastuzumab.
3. Determine the molecular predictors of complete magnetic resonance imaging radiologic response to a neoadjuvant anthracycline-based regimen when gene expression profiling is performed in a sequential, real-time fashion.

Entry Criteria

Disease Characteristics:

• Histologically confirmed newly diagnosed adenocarcinoma of the breast by core needle biopsy, incisional biopsy, or fine needle aspiration (FNA)
  • Incisional biopsy must result in < 10% removal of gross residual disease
• Measurable disease
  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

  OR

• Nonmeasurable disease
• Meets one of the following staging criteria:
  • Stage II or III disease
  • T4, any N, M0, including clinical or pathologic inflammatory disease
  • Regional stage IV disease where supraclavicular/infraclavicular lymph nodes are only site of metastasis
• No clinical or imaging evidence of distant metastasis
• Metaplastic carcinomas allowed
• Synchronous bilateral primaries allowed if the more advanced tumor meets staging criteria
• Patients for whom FNA was used to confirm initial diagnosis must have histologically confirmed invasive carcinoma by the start of chemotherapy
• Her-2/neu status known
• Currently receiving neoadjuvant chemotherapy consisting of a taxane-based regimen alone or followed by an anthracycline-based regimen
• Concurrent enrollment in the ACRIN-6657/CALGB-150012 imaging protocol required
• Hormone receptor status:
  • Any estrogen receptor or progesterone receptor status

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy to the ipsilateral breast for this malignancy

Endocrine therapy

• At least 4 weeks since prior tamoxifen or raloxifene

Radiotherapy

• No prior radiotherapy to the ipsilateral breast for this malignancy

Surgery

• Not specified

Other

• No other prior cytotoxic regimens

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No uncontrolled or severe cardiovascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• No ferromagnetic prostheses including the following:
  • Metallic implants not compatible with a magnetic resonance imaging machine
  • Heart valves
  • Aneurysm clips
  • Orthopedic prosthesis
  • Any metallic fragments anywhere in the body

Expected Enrollment

A total of 384 patients will be accrued for this study within 3 years.

Outline

This is a diagnostic, multicenter study conducted concurrently with CALGB-150012/ACRIN-6657 imaging protocol and concurrently with neoadjuvant anthracycline-based chemotherapy.

Patients receive an injection of gadopentetate dimeglumine and undergo magnetic resonance imaging (MRI) of the breast before initiation, 1-3 days after initiation, and then after completion of neoadjuvant anthracycline-based chemotherapy and prior to surgery. Patients who previously received a taxane also undergo an additional contrast-enhanced MRI scan.

Patients undergo biopsies before initiation and at the time of surgery. Patients also undergo blood draws at the time of the first biopsy and prior to surgery. Serum and tissue samples are used to assess biomarkers of genetic instability, cell cycle progression and cellular proliferation as predictors for anthracycline responsiveness, markers of apoptotic potential as predictors for taxane responsiveness in vivo, angiogenesis, hormone receptors, and molecular profiles using immunohistochemical methods.

Mammograms and possibly ultrasounds are performed prior to and after chemotherapy (before surgery).

Patients are followed every 6 months for 5 years and then annually for up to 10 years.

Esserman LJ, Perou C, Cheang M, et al.: Breast cancer molecular profiles and tumor response of neoadjuvant doxorubicin and paclitaxel: The I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657). [Abstract] J Clin Oncol 27 (Suppl 15): A-LBA515, 2009.

Hylton N, Blume J, Gatsonis C, et al.: MRI tumor volume for predicting response to neoadjuvant chemotherapy in locally advanced breast cancer: findings from ACRIN 6657/CALGB 150007. [Abstract] J Clin Oncol 27 (Suppl 15): A-529, 2009.

Lin C, Moore D, DeMichele A, et al.: Detection of locally advanced breast cancer in the I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657) in the interval between routine screening. [Abstract] J Clin Oncol 27 (Suppl 15): A-1503, 2009.

Pradhan SM, Carey L, Edmiston S, et al.: P53 mutation and differential response to neoadjuvant chemotherapy in women with locally advanced breast cancer: results from the I-SPY trial (CALGB 150007/1500012 and ACRIN 6657). [Abstract] J Clin Oncol 27 (Suppl 15): A-11099, 2009.

Gomez RE, Zakhireh J, Moore D, et al.: Sentinel node biopsy performed in the neoadjuvant setting for breast cancer: results from the I-SPY TRIAL (CALGB 150007/150012 & ACRIN 6657). [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-202, 2008.

Livasy C, Carey L, DeMichele A, et al.: Influence of anthracycline- and taxane-based neoadjuvant chemotherapy on tumor HER2 protein expression in locally advanced breast cancers: results from the I-SPY TRIAL (CALGB 150007/150012 & ACRIN 6657). [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-703, 2008.

Livasy C, Carey L, DeMichele A, et al.: Biomarkers associated with pathologic complete response to neoadjuvant chemotherapy in women with locally advanced breast cancer: results from the I-SPY TRIAL (CALGB 150007/150012 & ACRIN 6657). [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-5102, 2008.

Conway K, Edmiston SN, Tolbert D, et al.: Preliminary evaluation of p53 mutation type, tumor characteristics and clinical response among neoadjuvantly treated breast cancer patients in I-SPY1 (CALGB 150007/ACRIN 6657). [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3029, S134, 2006.

Esserman LJ, van't Veer LJ, Perou C, et al.: Biology of breast cancers that present as interval cancers and at young age should inform how we approach early detection and prevention. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-6034, 2008.

Carey LA, Oh D, Sawyer L, et al.: Gene expression subtype and p53 mutational status are correlated among neoadjuvantly treated breast cancers in UNC LCCC9819 and I-SPY1 (CALGB 150007/ACRIN 6657). [Abstract] J Clin Oncol 24 (Suppl 18): A-10048, 552s, 2006.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Laura Esserman, MD, MBA, Protocol chair		Ph: 415-885-7691; 800-888-8664

U.S.A.
California
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
Illinois
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Clinical Trials Office - Masonic Cancer Center at University of Minnesota	Ph:  612-624-2620
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Clinical Trials Office - Lineberger Comprehensive Cancer Center	Ph:  877-668-0683; 919-966-4432
Texas
	Dallas
	Parkland Memorial Hospital
		Thomas Weatherall, Jr.	Ph:  214-590-5582
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Clinical Trials Office - Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Ph:  866-460-4673; 214-648-7097

Related Information

PDQ® clinical trial CLB-49808
PDQ® clinical trial ACRIN-6657

Registry Information
Official Title		Contrast-Enhanced Breast MRI, MRS, And Correlative Science Studies To Characterize Tumor Response In Patients Undergoing Neoadjuvant Treatment For Locally Advanced Breast Cancer
Trial Start Date		2002-02-01
Trial Completion Date		2005-06-05 (estimated)
Registered in ClinicalTrials.gov		NCT00033397
Date Submitted to PDQ		2002-02-28
Information Last Verified		2009-11-13
NCI Grant/Contract Number		CA31946

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