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

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ClinicalTrials.gov Identifier: NCT02926911
Recruitment Status : Active, not recruiting
First Posted : October 6, 2016
Last Update Posted : March 1, 2024
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Duke University
Dana-Farber Cancer Institute
M.D. Anderson Cancer Center
New York University
Washington University School of Medicine
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
DCIS Ductal Carcinoma in Situ Other: Surgery Other: Active Monitoring Not Applicable

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 997 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS: A Phase III Prospective Randomized Trial
Actual Study Start Date : February 22, 2017
Estimated Primary Completion Date : July 2028
Estimated Study Completion Date : July 2028
Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Surgery
DCIS - Surgery +/- radiation choice for endocrine therapy (MMG q 12 months x 5 years usual care for recurrent disease)
 Other: Surgery
Surgery +/- radiation choice for endocrine therapy
Experimental: Active Monitoring
DCIS - Choice for endocrine therapy (MMG q 6 months x 5 years GCC for invasive progression)
 Other: Active Monitoring
Choice for endocrine therapy


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of new diagnoses of ipsilateral invasive cancer in surgery and AM arms at 2 years of follow up [ Time Frame: At 2 years follow-up ]
    To compare the number of patients that develop ipsilateral invasive cancer that received surgery to the number of patients that were placed on active monitoring after 2 years of follow-up


Secondary Outcome Measures :
  1. Quality of Life (QOL) [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Measured by Short Form (SF)-36

  2. Psychological outcomes [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Measured by five dimensions questionnaire (EQ-5D)

  3. Generalized anxiety [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Measured by the State Trait Anxiety Inventory (STAI) scale

  4. Generalized Depression [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Measured by the Center for Epidemiologic Studies Depression Scale (CES-D) 10

  5. Coping [ Time Frame: Baseline ]
    Coping evaluated using the Brief COPE, a shortened form of the COPE Inventory, inclusive of 28 items (14 subscales).

  6. Intolerance of uncertainty [ Time Frame: Baseline and at 2 years ]
    Assessment of feelings of uncertainty using the Intolerance of Uncertainty Scale (Short-form), which has been used in studies of active monitoring in the prostate cancer setting.

  7. Mastectomy rate [ Time Frame: 2, 5, and 7 year follow-up ]
    To compare the impact of surgery vs. AM on the number of mastectomies performed in patients with DCIS

  8. Breast conservation rate [ Time Frame: 2, 5, and 7 year follow-up ]
    To compare the impact of surgery vs. AM on the number of breast conservation surgeries performed in patients with DCIS

  9. Contralateral invasive cancer rate [ Time Frame: 2, 5, and 7 year follow-up ]
    To compare the impact of surgery vs. AM on the rate of development of contralateral invasive cancer in patients with DCIS

  10. Overall survival rate [ Time Frame: 2, 5, and 7 year follow-up ]
    To compare the impact of surgery vs. AM on the overall survival rate in patients with DCIS

  11. Breast cancer specific survival rate [ Time Frame: 2, 5, and 7 year follow-up ]
    To compare the impact of surgery vs. AM on the breast cancer specific survival rate in patients with DCIS

  12. Ipsilateral invasive cancer rate in surgery arm at 5 and 7 year follow-up [ Time Frame: 5 and 7 year follow-up ]
    To determine the number of DCIS patients in the surgery arm that develop ipsilateral invasive cancer

  13. Ipsilateral invasive cancer rate in AM arm [ Time Frame: 5 and 7 year follow-up ]
    To determine the number of DCIS patients in the AM arm that develop ipsilateral invasive cancer


Other Outcome Measures:
  1. Breast MRI utilization rate [ Time Frame: 2, 5, and 7 year follow-up ]
    Determine the rate of use of breast MRI imaging compared to use of other breast imaging techniques

  2. Breast biopsy rate [ Time Frame: 2, 5, and 7 year follow-up ]
    Determine the rate of biopsies performed during follow-up of patients with DCIS

  3. Radiation rate [ Time Frame: 2, 5, and 7 year follow-up ]
    Determine the rate of the performance of radiation therapy on patients with DCIS

  4. Chemotherapy rate [ Time Frame: 2, 5, and 7 year follow-up ]
    Determine the rate of the use of chemotherapy on patients with DCIS

  5. Self-reported co-morbidity [ Time Frame: 6 months, 1 year, and once a year (years 2 through 5) ]
    Self-reported diary

  6. Adherence to hormonal therapy [ Time Frame: 6 months, 1 year, and once a year (years 2 through 5) ]
    Evaluated with a drug diary

  7. Symptoms [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    A modified 19-item version of the Breast Cancer Prevention Trial (BCPT) Symptom Checklist will evaluate commonly reported menopausal symptoms

  8. General pain [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Evaluated with the Brief Pain Inventory, a well-validated general measure of pain and disability worst pain, least pain, and interference

  9. Breast specific pain [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Breast specific pain will be measured by the Breast Cancer Pain Questionnaire (BCPQ); the BCPQ includes assessment of pain severity, pain frequency (how many days/week), and pain location (breast, arm, side, axilla), from which a Pain Burden Index (PBI) can be calculated

  10. Body image [ Time Frame: Baseline, 6 months, 1 year, and once a year (years 2 through 5) ]
    Body image will be evaluated by the Breast-Questionnaire, a validated instrument to evaluate outcomes following surgery, will be used to evaluate satisfaction with body image

  11. Decisional regret [ Time Frame: Years 1 through 5 ]
    The Decision Regret Scale will measure how women perceived their DCIS treatment decision. The SURE scale, which is composed of four items from the Decisional Conflict Scale will be used to measure patients' uncertainty about which treatment to choose and factors contributing to uncertainty (feeling uninformed, unclear values, and unsupported in decision-making).

  12. Knowledge [ Time Frame: Baseline and 2 years ]
    DCIS and breast cancer knowledge will be measured with items adapted from the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI) as well as questions developed specifically for a study that assessed DCIS knowledge and risk perceptions. The investigators will assess risk perceptions in women with DCIS using questions developed by Lerman and Croyle that will measure risk perceptions in relation to psychosocial outcomes in women with DCIS

  13. Risk perceptions [ Time Frame: Baseline and 2 years ]
    Measured by the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI)

  14. Communication with physicians [ Time Frame: Baseline ]
    To assess communication with physicians about DCIS management options, the investigators will adapt items used in a prior study of surgical decision-making, including the extent to which their physician talked to them about AM vs. surgery. Additionally the investigators will ask about sources of information for the management of their DCIS

  15. Financial burden [ Time Frame: 6 months ]
    The investigators will adapt items from the National Health Interview Survey and the Cancer Outcomes Research and Surveillance (CanCORS) Study to assess financial burden. The investigators will also ask women to Cancer Care estimate out of pocket expenses attributed to their DCIS diagnosis.

  16. Employment status [ Time Frame: Baseline, 6 months, year 1, and once a year (years 1 through 5) ]
    Employment status will be assessed using a measure that is being added to the Alliance Patient Questionnaire as it has been tested and validated in breast cancer populations.

  17. Concerns about future breast events [ Time Frame: Baseline and 2 years ]
    Four items from the Quality of Life in Adult Cancer Survivors (QLACS) scale will be adapted to evaluate frequency (1=never; 7=always) of worries about DCIS, including concerns about future breast events and death from DCIS


Eligibility Criteria
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Ages Eligible for Study:   40 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02926911


Locations
Show Show 141 study locations
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Patient-Centered Outcomes Research Institute
Duke University
Dana-Farber Cancer Institute
M.D. Anderson Cancer Center
New York University
Washington University School of Medicine
Investigators
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Principal Investigator: Shelley Hwang, MD, MPH Duke University
Study Chair: Ann Partridge, MD, MPH Dana-Farber Cancer Institute
Study Chair: Alastair Thompson, MD Baylor College of Medicine
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT02926911    
Other Study ID Numbers: AFT-25
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: March 1, 2024
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient medical information both, associated with biologic specimens or not, is confidential and may only be disclosed to third parties as permitted by the Informed Consent Form (ICF) (or separate authorization for use and disclosure of personal health information) which has been signed by the patient, unless permitted or required by law. Data derived from biologic specimen analysis on individual patients will in generally not be provided to study investigators unless a request for research use is granted. The overall results of any research conducted using biologic specimens will be available in accordance with the effective Alliance Foundation Trial (AFT) policy on study data publication.
Time Frame: Data will become available July 2023, no end date.
Access Criteria: following a formal request by an investigator to and approval from AFT

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alliance Foundation Trials, LLC.:
Ductal Carcinoma
Additional relevant MeSH terms:
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Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Carcinoma
Neoplasms, Glandular and Epithelial
 Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Carcinoma In Situ