MRI and Gene Expression in Diagnosing Patients With Ductal Breast Cancer In Situ

Ductal Breast Carcinoma In Situ Clinical Trial

Official title:

Prospective Study of Magnetic Resonance Imaging (MRI) and Multiparameter Gene Expression Assay in Ductal Carcinoma In Situ (DCIS)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02352883
• Other study ID #: E4112
• Secondary ID: NCI-2014-01261E4
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 25, 2015
• Est. completion date: November 2027

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial studies magnetic resonance imaging (MRI) and gene expression in diagnosing patients with abnormal cells in the breast duct that have not spread outside the duct. MRI uses radio waves and a powerful magnet linked to a computer to create detailed pictures of areas inside the body. MRI may help find and diagnose patients with breast cancer. It may also help doctors predict a patient's response to treatment and help plan the best treatment. Genetic studies may help doctors predict the outcome of treatment and the risk for disease recurrence. Performing MRI with genetic studies may help determine the best treatment for patients with breast cancer in situ.

Description:

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with ductal carcinoma in situ (DCIS) diagnosed on core needle biopsy judged to be breast conservation candidates based upon standard imaging (mammography +/- sonography) and physical examination (a) who convert to mastectomy in step 1 based on MRI findings, and (b) who have a mastectomy as the final surgical procedure in step 2.

SECONDARY OBJECTIVES:

I. To assess the relation between baseline clinical covariates (e.g., tumor grade, necrosis, histologic type, mammographic lesion size), MRI morphologic and kinetic features, and the DCIS score.

II. To assess the diagnostic accuracy of MRI in extent of disease evaluation in patients with DCIS.

III. To estimate the proportion of patients who require re-operation because of inadequate excision after MRI.

IV. To estimate the proportion of patients who proceed to mastectomy after an initial attempt at wide local excision because of either inadequate tumor-free margins (< 2 mm), or other reasons.

V. To estimate the 5-year and 10-year ipsilateral breast event (in situ and invasive) rate (IBE) among women with DCIS assessed with MRI preoperatively and treated with wide local excision without radiation therapy (if there is a low DCIS score) or with radiation therapy (if there is an intermediate-high DCIS score).

VI. To estimate the proportion of women with DCIS who receive treatment that is concordant with their treatment goals and concerns.

VII. To estimate the proportion of women with DCIS whose decision autonomy preference was concordant with perceived level of decision involvement.

VIII. To assess decision quality using knowledge score and decision process. IX. To assess concordance between decision autonomy preference and perceived level of decision involvement, knowledge and decision process scores as independent predictors of decision satisfaction at the first post-operative visit.

X. To assess the relationship of patient-reported outcomes and disease-specific covariates, and quality of life after treatment.

XI. To assess the role of disease status, diagnostic test results and surgeon recommendation as predictors of treatment received.

XII. To compare the patient-reported diagnostic testing burden of bilateral mammography and MRI as measured by Testing Morbidities Index (TMI).

OUTLINE:

STEP 1:

ARM A: Patients undergo MRI prior to surgery. Patients undergo additional imaging and/or biopsies if indicated based on MRI.

STEP 2: Patients are assigned to 1 of 2 treatment arms based on the results of the MRI.

ARM B: Patients undergo a mastectomy. Patients do not register for Step 3.

ARM C: Patients undergo wide local excision +/- re-excision. Patients may cross-over to Arm B if mastectomy is indicated. Tissue samples collected during surgery are used to calculate the DCIS score using genetic analysis testing. Patients may then proceed to Step 3.

STEP 3: Patients are assigned to 1 of 2 treatment arms based on the results of the DCIS score test.

ARM D (DCIS score < 39): Patients undergo endocrine therapy as directed.

ARM E (DCIS score >= 39): Patients undergo radiation therapy and endocrine therapy as directed.

After completion of study treatment, patients are followed up every 6 months for 5 years and then every 12 months for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 368
• Est. completion date: November 2027
• Est. primary completion date: November 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Registration to Step 1:

• Patients must have pathologically confirmed diagnosis of unilateral ductal carcinoma in situ with no evidence of microinvasive or invasive disease obtained by core needle biopsy within 4 months of registration; patients diagnosed by surgical excision are not eligible; patients with synchronous bilateral disease are not eligible; patients with synchronous bilateral disease (i.e., synchronous DCIS or invasive cancer) are not eligible

• Patients will be staged prior to registration according to the clinical staging criteria adapted from the American Joint Committee on Cancer (AJCC) Cancer Staging Data Forms of the AJCC Cancer Staging Manual, 7th Edition, 2009; Note: For consistency purposes, AJCC 7th Edition will continue to be used throughout the entire study enrollment period

• Required studies include a bilateral screening mammogram within 6 months and diagnostic mammogram of the affected breast within 3 months prior to registration

• Patients must not have previous ipsilateral invasive breast cancer or DCIS

• Patients must not have known deleterious mutations in breast cancer (BRCA) genes

• Patients must not have received hormonal therapy (i.e., tamoxifen, raloxifene, and/or aromatase inhibitors) for prevention of breast cancer within 3 months of the biopsy documenting DCIS

• Patients must not have history of chemotherapy for cancer within 6 months prior to registration

• No prior history of breast radiotherapy that will prevent the use of radiotherapy for the present DCIS

• Patients must be judged to be suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):

• No history of untreatable claustrophobia;

• No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants);

• No history of sickle cell disease;

• No contraindication to intravenous contrast administration;

• No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance;

• No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) < 30 mL/min/1.73 m^2 based on a serum creatinine level obtained within 28 days prior to registration;

• Weight lower than that allowable by the MRI table;

• No prior MRI of the breasts within the 6 months prior to registration

• Patients must be eligible for breast-conserving therapy (BCT) based on clinical examination and mammography; if ultrasound is performed, findings must also be consistent with eligibility for BCT

• Patients must not have multicentric disease scheduled to undergo multiple lumpectomies; multifocal disease that can be encompassed in a single operative bed are eligible

• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 3 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study

• Registration to Step 2:

• MRI has been performed in Step 1, and additional imaging studies and biopsies performed if indicated

• The clinician/patient has made the decision as to whether the patient will proceed to wide local excision or mastectomy

• Registration to Step 3:

• Patient's most recent surgery was wide local excision with or without re-excision and for which there was obtained clear (>= 2 mm) margins at breast conserving surgery, and the pathology reveals pure DCIS; patients with invasive cancer or DCIS with microinvasion will not be registered on step 3, but will be followed for clinical outcomes

• The OncotypeDX Patient Report of the DCIS Score from the OncotypeDX Breast Cancer Assay performed by Genomic Health on the excision tissue have been uploaded by the site into the Rave electronic case report forms (eCRF)

Related Conditions & MeSH terms

• Breast Carcinoma In Situ
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating
• Ductal Breast Carcinoma In Situ

Intervention

Procedure:
• Magnetic Resonance Imaging
Undergo MRI
• Therapeutic Conventional Surgery
Undergo mastectomy
• Therapeutic Surgical Procedure
Undergo wide local excision

Radiation:
• Radiation Therapy
Undergo radiation therapy

Drug:
• Endocrine Therapy
Undergo endocrine therapy

Other:
• Quality-of-Life Assessment
Ancillary studies
• Laboratory Biomarker Analysis
Correlative studies
• Cytology Specimen Collection Procedure
Correlative studies

Locations

Country	Name	City	State
United States	Cancer Care of Western North Carolina	Asheville	North Carolina
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	John Fitzgerald Kennedy Medical Center	Atlantis	Florida
United States	IU Health West Hospital	Avon	Indiana
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Medical Oncology LLC	Baton Rouge	Louisiana
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Aultman Health Foundation	Canton	Ohio
United States	Northwestern University	Chicago	Illinois
United States	The Christ Hospital	Cincinnati	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Easton Hospital	Easton	Pennsylvania
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Greenwich Hospital	Greenwich	Connecticut
United States	Hartford Hospital	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	Midstate Medical Center	Meriden	Connecticut
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Regional Hematology and Oncology PA	Newark	Delaware
United States	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin
United States	Owensboro Health Mitchell Memorial Cancer Center	Owensboro	Kentucky
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Pottstown Memorial Medical Center	Pottstown	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Roger Williams Medical Center	Providence	Rhode Island
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Clinic	Springfield	Illinois
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients judged to be breast conservation candidates based upon standard imaging and physical examination who convert to mastectomy in step 1 based on MRI findings		After MRI (within 30 days following study entry), and prior to surgery
Primary	Proportion of patients judged to be breast conservation candidates based upon standard imaging and physical examination who have a mastectomy as the final surgical procedure in step 2		Up to 12 months post-op
Secondary	Factors associated with DCIS score	The relation between baseline clinical covariates (tumor grade, necrosis, histologic type, mammographic lesion size), MRI morphologic and kinetic features, and the DCIS score will be assessed.	After surgery (DCIS Score is determined from surgical specimen)
Secondary	Diagnostic accuracy of MRI in extent of disease evaluation in patients with DCIS		Up to 12 months post-op
Secondary	Proportion of patients who require re-operation because of inadequate excision after MRI	A two-sided 95% Wilson confidence interval will be derived.	Up to 12 months post-op
Secondary	Proportion of patients who proceed to mastectomy after an initial attempt at wide local excision because of either inadequate tumor-free margins (< 2mm), or other reasons	A two-sided 95% Wilson confidence interval will be derived. In addition to the overall probability of conversion in this cohort, estimates will be stratified by the reason for conversion.	Up to 12 months post-op
Secondary	IBE rate	Kaplan-Meier curves will be derived for the time to ipsilateral breast event for patients assigned to be treated with RT and those not treated with RT. Point estimates and 95% two-sided confidence intervals will be developed.	At 5 years
Secondary	IBE rate	Kaplan-Meier curves will be derived for the time to ipsilateral breast event for patients assigned to be treated with RT and those not treated with RT. Point estimates and 95% two-sided confidence intervals will be developed.	At 10 years
Secondary	Proportion of women who receive treatment that is concordant with their treatment goals and concerns	The proportion of patients with concordant care will be calculated and a 95% Wilson confidence interval will also be derived.	Up to 24 months post-op
Secondary	Proportion of women whose decision autonomy preference was concordant with perceived level of decision involvement	Concordance will be defined as an exact match between decision autonomy preference (patient-based, shared, surgeon-based) and perceived level of decision involvement (patient based, shared, surgeon-based) as assessed by the Control Preferences Scale, reduced to three categories. The proportion of patients with concordance will be calculated for the sample. In addition, the degree of concordance over the group will be determined using kappa analysis.	Up to 5 days after pre-surgical consultation
Secondary	Decision quality, assessed using the composite of knowledge score and decision process score	To calculate knowledge score, a point for each correct answer on the knowledge questionnaire will be assigned, with missing responses receiving 0 points. A total score will be calculated for all patients who complete at least half of the items and scaled from 0-100%. To calculate a decision process score, a point will be assigned for each "yes" or "a lot/some" response. The sum will be scaled from 0-100%. The average of the two scores will be used as the outcome measure.	Up to 5 days after pre-surgical consultation
Secondary	Role of concordance between decision autonomy preference and perceived level of decision involvement, knowledge and decision process scores as independent predictors of decision satisfaction	Linear regression modeling will be used in which the response variable will be decision satisfaction. The independent variables will be the indicator of concordance between decision autonomy preference and perceived level of decision involvement, the knowledge score and the decision process score. Two-way interactions between predictors will also be examined.	Assessed via questionnaire administered at first post-operative visit
Secondary	Patient-reported quality of life, measured using the Patient Reported Outcomes Measurement Information System (PROMIS)10 instrument	The relationship of patient-reported outcomes and disease specific covariates, and quality of life will be assessed.	At 12 months post-op
Secondary	Patient-reported quality of life, measured using the PROMIS10 instrument	The relationship of patient-reported outcomes and disease specific covariates, and quality of life will be assessed.	At 24 months post-op
Secondary	Role of disease status, diagnostic test results, and surgeon recommendation as predictors of treatment received	Logistic regression modeling will be used in which the response variable will be the indicator of conversion to mastectomy (vs lumpectomy). The independent variables will include covariates describing disease status at baseline, MRI results, surgeon recommendation, patient decision involvement (such as the decision autonomy preference scale) and treatment concerns (as measured via the 7-item questionnaire). Separate analyses will be performed for conversion to mastectomy directly post MRI and conversion to mastectomy following BCS as the response variable.	Up to 24 months post-op
Secondary	Patient-reported diagnostic testing burden of bilateral mammogram, MRI, and biopsies, measured by TMI	A Wilcoxon signed rank test will be used to compare TMI scores for mammography and MRI. In a secondary analysis regression modeling will be used to examine the effects of patient characteristics on the patient's perception of diagnostic test burden for the two modalities.	Up to 5 days after pre-surgical consultation