Clinical trial NCT02352883: MRI and Gene Expression in Diagnosing Patients With Ductal Breast Cancer In Situ
Official title: Prospective Study of Magnetic Resonance Imaging (MRI) and Multiparameter Gene Expression Assay in Ductal Carcinoma In Situ (DCIS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Ductal Breast Carcinoma In Situ
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2015-02-02
Enrollment: 368
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: After MRI (within 30 days following study entry), and prior to surgery
measure: 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
timeFrame: Up to 12 months post-op
Secondary outcomes:
measure: Factors associated with DCIS score
timeFrame: After surgery (DCIS Score is determined from surgical specimen)
measure: Diagnostic accuracy of MRI in extent of disease evaluation in patients with DCIS
timeFrame: Up to 12 months post-op
measure: Proportion of patients who require re-operation because of inadequate excision after MRI
timeFrame: Up to 12 months post-op
measure: 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
timeFrame: Up to 12 months post-op
measure: IBE rate
timeFrame: At 5 years
measure: IBE rate
timeFrame: At 10 years
measure: Proportion of women who receive treatment that is concordant with their treatment goals and concerns
timeFrame: Up to 24 months post-op
measure: Proportion of women whose decision autonomy preference was concordant with perceived level of decision involvement
timeFrame: Up to 5 days after pre-surgical consultation
measure: Decision quality, assessed using the composite of knowledge score and decision process score
timeFrame: Up to 5 days after pre-surgical consultation
measure: Role of concordance between decision autonomy preference and perceived level of decision involvement, knowledge and decision process scores as independent predictors of decision satisfaction
timeFrame: Assessed via questionnaire administered at first post-operative visit
measure: Patient-reported quality of life, measured using the Patient Reported Outcomes Measurement Information System (PROMIS)10 instrument
timeFrame: At 12 months post-op
measure: Patient-reported quality of life, measured using the PROMIS10 instrument
timeFrame: At 24 months post-op
measure: Role of disease status, diagnostic test results, and surgeon recommendation as predictors of treatment received
timeFrame: Up to 24 months post-op
measure: Patient-reported diagnostic testing burden of bilateral mammogram, MRI, and biopsies, measured by TMI
timeFrame: Up to 5 days after pre-surgical consultation
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Kaiser Permanente-San Diego Zion
state: California
city: San Marcos
country: United States
facility: Kaiser Permanente-San Marcos
state: California
city: Greenwich
country: United States
facility: Greenwich Hospital
state: Connecticut
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Meriden
country: United States
facility: Midstate Medical Center
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Newark
country: United States
facility: Regional Hematology and Oncology PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Atlantis
country: United States
facility: John Fitzgerald Kennedy Medical Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital/Cancer Center
state: Illinois
city: Plainfield
country: United States
facility: Edward Hospital/Cancer Center?Plainfield
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Avon
country: United States
facility: IU Health West Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Mishawaka
country: United States
facility: Memorial Regional Cancer Center Day Road
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Main Office
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Owensboro
country: United States
facility: Owensboro Health Mitchell Memorial Cancer Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Louisiana Hematology Oncology Associates LLC
state: Louisiana
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Baton Rouge
country: United States
facility: Medical Oncology LLC
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Salisbury
country: United States
facility: Peninsula Regional Medical Center
state: Maryland
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Flemington
country: United States
facility: Hunterdon Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
state: New Jersey
city: Somerville
country: United States
facility: Robert Wood Johnson University Hospital Somerset
state: New Jersey
city: Voorhees
country: United States
facility: Virtua West Jersey Hospital Voorhees
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Asheville
country: United States
facility: Cancer Care of Western North Carolina
state: North Carolina
city: Asheville
country: United States
facility: Mission Hospital-Memorial Campus
state: North Carolina
city: Asheville
country: United States
facility: Hope Women's Cancer Centers-Asheville
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Canton
country: United States
facility: Aultman Health Foundation
state: Ohio
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Easton
country: United States
facility: Easton Hospital
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Media
country: United States
facility: Riddle Memorial Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Phoenixville
country: United States
facility: Phoenixville Hospital
state: Pennsylvania
city: Pottstown
country: United States
facility: Pottstown Memorial Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health-York Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Oconomowoc
country: United States
facility: Oconomowoc Memorial Hospital-ProHealth Care Inc
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: Constance Lehman
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lehman CD, Gatsonis C, Romanoff J, Khan SA, Carlos R, Solin LJ, Badve S, McCaskill-Stevens W, Corsetti RL, Rahbar H, Spell DW, Blankstein KB, Han LK, Sabol JL, Bumberry JR, Gareen I, Snyder BS, Wagner LI, Miller KD, Sparano JA, Comstock C. Association of Magnetic Resonance Imaging and a 12-Gene Expression Assay With Breast Ductal Carcinoma In Situ Treatment. JAMA Oncol. 2019 Jul 1;5(7):1036-1042. doi: 10.1001/jamaoncol.2018.6269.