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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00033397
• Other study ID #: CALGB-150007
• Secondary ID: CALGB-150007CDR0
• Status: Completed
• Phase: N/A
• First received: April 9, 2002
• Last updated: July 11, 2017
• Start date: February 2002
• Est. completion date: May 1, 2012

Study information

• Verified date: July 2017
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

RATIONALE: Comparing results of diagnostic procedures performed before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the most effective treatment.

PURPOSE: Diagnostic trial to study magnetic resonance imaging (MRI) and biomarkers in women who are receiving chemotherapy before surgery for locally advanced breast cancer.

Description:

OBJECTIVES:

Primary

• Support accrual to the ACRIN-6657/CALGB-150012 magnetic resonance imaging (MRI) correlative science study.

• 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.

• Identify two groups of participants who have statistically different 3-year DFS, based on 1 or more biomarkers, including MRI.

• 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.

• Determine whether molecular markers are associated with specific imaging patterns seen on MRI of these patients.

• Predict response with MRI results and marker data from cell cycle check points, proliferation, angiogenesis, hormone receptors, and molecular profiles in these patients.

Secondary

• 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.

• 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.

• 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.

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: May 1, 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female 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

PRIOR CONCURRENT THERAPY:

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

Other

• No other prior cytotoxic regimens

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• biopsy

• magnetic resonance imaging

• radiomammography

• ultrasound imaging

Radiation:
• gadopentetate dimeglumine

Drug:
• chemotherapy

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (15)

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.

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 1

Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, DeMichele A, Gray JW, Conway-Dorsey K, Lenburg ME, Buxton MB, Davis SE, van't Veer LJ, Hudis C, Chin K, Wolf D, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpe — View Citation

Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C, Livasy C, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen — View Citation

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.

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-

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

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, Buxton MB, Moore D, Krontiras H, Carey L, DeMichele A, Montgomery L, Tripathy D, Lehman C, Liu M, Olapade O, Yau C, Berry D, Esserman LJ; I-SPY TRIAL Investigators. Locally advanced breast cancers are more likely to present as Interval Cancers: res — View Citation

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.

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 Annu

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]

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

Van 't Veer LJ, Das D, DeMichele A, et al.: Neoadjuvant response in the context of a biologically defined low or high risk tumor has a different clinical consequence, the I-SPY trial (CALGB 150007/150012, ACRIN 6657). [Abstract] 32nd Annual San Antonio Br

Wolf DM, Das D, Lenburg ME, et al.: From the lab to the clinic: gene-expression profiles that are associated with Mek-inhibitor sensitivity in vitro are coordinately co-expressed in breast cancer biopsy samples from the I-SPY Trial (CALGB 150007/150012, A

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response		Up to 5 years