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Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS

Trial Status: Active

This study looks at the risks and benefits of active monitoring (AM) compared to surgery in the setting of a pragmatic prospective randomized trial for low risk DCIS. Our overarching hypothesis is that management of low-risk Ductal Carcinoma in Situ (DCIS) using an AM approach does not yield inferior cancer or quality of life outcomes compared to surgery.

Inclusion Criteria

  • Diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCIS without invasive breast cancer (date of diagnosis defined as the date of the first pathology report that diagnosed the patient with DCIS) OR: atypia verging on DCIS OR: DCIS + LCIS (mix and/or separate locations in the same breast)
  • A patient who has had a lumpectomy or partial mastectomy with margins positive for DCIS (i.e. <2mm/ink on tumor) as part of their treatment for a current DCIS diagnosis is also eligible (post-excision bilateral mammogram required at enrollment to establish a new baseline)
  • No previous DCIS or invasive breast cancer in ipsilateral breast 5 years prior to current DCIS diagnosis
  • 40 years of age or older at time of DCIS diagnosis
  • ECOG performance status 0 or 1
  • No contraindication for surgery
  • Baseline imaging (must include dimensions):
  • Unilateral DCIS: contralateral normal mammogram ≤ 6 months of registration and ipsilateral breast imaging ≤ 120 days of registration (must include ipsilateral mammogram; can also include ultrasound or breast MRI)
  • Bilateral DCIS: bilateral breast imaging ≤ 120 days of registration (must include bilateral mammogram; can also include ultrasound or breast MRI)
  • DCIS s/p lumpectomy: post excision mammogram on side of excision ≤ 60 days of registration
  • Pathologic criteria:
  • Any grade I DCIS (irrespective of necrosis/comedonecrosis)
  • Any grade II DCIS (irrespective of necrosis/comedonecrosis)
  • Absence of invasion or microinvasion
  • Diagnosis of DCIS confirmed on core needle biopsy, vacuum-assisted or surgery ≤ 120 days of registration
  • ER(+) and/or PR(+) by IHC (≥ 10% staining or Allred score ≥ 4) unless atypia verging on DCIS in which case biomarker criterion does not apply
  • HER2 0, 1+, or 2+ by IHC if HER2 testing is performed
  • Histology slides reviewed and agreement between two clinical pathologists (not required to be at same institution) that pathology fulfills COMET eligibility criteria. In cases of disagreement between the two pathology reviews about whether or not a case fulfills the eligibility criteria, a third pathology review will be required.
  • At least two sites of biopsy for those cases where individual mammographic extent of calcifications exceeds 4 cm, with second biopsy benign or both sites fulfilling pathology eligibility criteria (ER/PR testing required for second biopsy)
  • Amenable to follow up examinations
  • Ability to read, understand and evaluate study materials and willingness to sign a written informed consent document
  • Reads and speaks Spanish or English

Exclusion Criteria

  • Male DCIS
  • Grade III DCIS
  • Concurrent diagnosis of invasive or microinvasive breast cancer in either breast
  • Documented mass on examination or mass/hypoechoic area on imaging at site of DCIS prior to biopsy yielding diagnosis of DCIS, with exception of: subsequent lumpectomy or partial mastectomy (with positive DCIS margins i.e. <2mm/ink on tumor) followed by a post-surgery MMG; fibroadenoma at a distinct/separate site from site of DCIS; or diagnosis of mass/hypoechoic area as a cyst or a papilloma. In cases of uncertainty about whether the mass was present on physical examination prior to biopsy, the following criteria should be applied: if mammogram noting abnormal findings is diagnostic MMG = symptomatic/if mammogram noting abnormal findings is screening MMG = asymptomatic. If a patient has a mass on imaging that is biopsied (worked-up) and does not show invasive breast cancer, they are eligible. If a patient has a mass on initial MMG that is not seen on subsequent MMG, they are eligible (if initial mass occurred due to additional work-up).
  • Any color/bloody nipple discharge (ipsilateral breast)
  • Mammographic finding of BIRADS 4 or greater within 6 months prior to registration at site of breast other than that of known DCIS, without pathologic assessment
  • Use of investigational cancer agents within 6 weeks prior to diagnosis of DCIS
  • Any serious and/or unstable pre-existing medical, psychiatric, or other existing condition that would prevent compliance with the trial or consent process
  • Pregnancy. If a woman has been confirmed as pregnant, she will not be eligible to take part in the trial. If she suspects there is a chance that she may be pregnant, a pregnancy test should be undertaken, although a pregnancy test for all women of child-bearing potential is not mandatory. In addition, if a woman becomes pregnant once registered to the trial, she can continue to be followed (endocrine therapy is not a mandatory requirement of the study)
  • Documented history of prior tamoxifen, aromatase inhibitor, or raloxifene use in the 6 months prior to registration
  • Current use of exogenous hormones (i.e. oral progesterone)

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE
MedStar Washington Hospital Center
Status: ACTIVE

Florida

Jacksonville
Mayo Clinic in Florida
Status: ACTIVE

Hawaii

Aiea
Pali Momi Medical Center
Status: ACTIVE
Honolulu
Kapiolani Medical Center for Women and Children
Status: ACTIVE
Straub Clinic and Hospital
Status: ACTIVE

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: APPROVED

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: ACTIVE

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: ACTIVE

Maryland

Baltimore
MedStar Franklin Square Medical Center / Weinberg Cancer Institute
Status: ACTIVE
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Nancy S. Tait
Phone: 410-328-3546
Email: ntait@umm.edu

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Milford
Dana-Farber / Brigham and Women's Cancer Center at Milford Regional
Status: ACTIVE
South Weymouth
Dana-Farber / Brigham and Women's Cancer Center at South Shore
Status: ACTIVE

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL_AND_INTERVENTION
Rochester
Mayo Clinic in Rochester
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

Nebraska

Omaha
University of Nebraska Medical Center
Status: ACTIVE

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: WITHDRAWN

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: ACTIVE
Santa Fe
Christus Saint Vincent Regional Cancer Center
Status: ACTIVE

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: ACTIVE
Buffalo
Roswell Park Cancer Institute
Status: WITHDRAWN
New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE
Durham
Duke University Medical Center
Status: ACTIVE
Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE

South Carolina

Charleston
Medical University of South Carolina
Status: ADMINISTRATIVELY_COMPLETE

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
M D Anderson Cancer Center
Status: ACTIVE

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

Virginia

Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: ACTIVE
Contact: Kimberly Garnett
Phone: 804-628-5810

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: ACTIVE

Overdiagnosis and overtreatment resulting from mammographic screening have been estimated to

be as high as 1 in 4 patients diagnosed with breast cancer although the absence of standard

definitions for measuring overdiagnosis has led to much uncertainty around this estimate. The

national health care expenditure resulting from false positive mammograms and breast cancer

overdiagnosis has been estimated to approach $4 billion annually. There is general consensus

that much of this burden derives from the treatment of DCIS; for those estimated 40,000 women

per year whose DCIS may never have progressed even without treatment, medical intervention

can only harm. In those women who undergo surgical management of DCIS, there is risk of

developing persistent pain at the surgical site, with estimates ranging from 25-68%.

Importantly, persistent pain after lumpectomy may be as prevalent as that after total

mastectomy. Persistent postsurgical pain is rated by patients as the most troubling symptom,

leading to disability and psychological distress, and is often resistant to management.

Although prospective population-based data have demonstrated significant patient and surgical

focus on pain with remarkably high levels of chronic pain 4 and 9 months after breast

surgery, much of these data have been collected in women with invasive cancer, with little

data directly relevant to patients with DCIS.

The overarching hypothesis of the study is that management of low-risk DCIS using an active

monitoring (AM) approach does not yield inferior cancer or quality of life outcomes compared

to surgery.

Trial Phase Phase NA

Trial Type Treatment

Lead Organization
Alliance Foundation Trials, LLC.

  • Primary ID AFT-25
  • Secondary IDs NCI-2017-00394
  • Clinicaltrials.gov ID NCT02926911