Clinical Trials /

Comparison of Operative to Monitoring and Endocrine Therapy (COMET) Trial For Low Risk DCIS

NCT02926911

Description:

This study looks at the risks and benefits of active surveillance (AS) compared to guideline concordant care (GCC) 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 AS approach does not yield inferior cancer or quality of life outcomes compared to GCC.

Related Conditions:
  • Ductal Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Comparison of Operative to Monitoring and Endocrine Therapy (COMET) Trial For Low Risk DCIS
  • Official Title: Comparison of Operative to Monitoring and Endocrine Therapy (COMET) Trial For Low Risk DCIS: A Phase III Prospective Randomized Trial

Clinical Trial IDs

  • ORG STUDY ID: AFT-25
  • NCT ID: NCT02926911

Conditions

  • DCIS
  • Ductal Carcinoma in Situ

Purpose

This study looks at the risks and benefits of active surveillance (AS) compared to guideline concordant care (GCC) 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 AS approach does not yield inferior cancer or quality of life outcomes compared to GCC.

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
      surveillance (AS) approach does not yield inferior cancer or quality of life outcomes
      compared to guideline concordant care (GCC).
    

Trial Arms

NameTypeDescriptionInterventions
Guideline Concordant CareActive ComparatorDCIS - Surgery +/- radiation choice for endocrine therapy (MMG q 12 months x 5 years usual care for recurrent disease)
    Active SurveillanceExperimentalDCIS - Choice for endocrine therapy (MMG q 6 months x 5 years GCC for invasive progression)

      Eligibility Criteria

              Inclusion Criteria:
      
                -  New diagnosis of DCIS without invasive cancer; date of diagnosis defined as the date
                   of the first pathology report that diagnosed the patient with DCIS
      
                -  Unilateral, bilateral, unifocal, or multifocal DCIS
      
                -  ADH/borderline DCIS
      
                -  A patient who has had a lumpectomy with positive margins as part of their treatment
                   for a current DCIS diagnosis is eligible (post-excision mammogram required at
                   enrollment to establish a new baseline)
      
                -  No previous history of breast cancer (DCIS or invasive cancer) in either breast 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:
      
                     -  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)
      
                -  Pathologic criteria:
      
                     -  Any grade I DCIS (irrespective of necrosis/comedonecrosis)
      
                     -  Any grade II DCIS (irrespective of necrosis/comedonecrosis)
      
                     -  Absence of invasion or microinvasion
      
                     -  Diagnosis confirmed on core needle, vacuum-assisted or surgery ≤ 120 days of
                        registration
      
                     -  ER(+) and/or PR(+) by IHC (≥ 10% staining or Allred score ≥ 4)
      
                     -  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 mammographic extent of
                   calcifications exceeds 4 cm, with second biopsy benign or both sites fulfilling
                   pathology eligibility criteria
      
                -  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 imaging at site of DCIS prior to biopsy yielding
                   diagnosis of DCIS, with exception of fibroadenoma at a distinct/separate site from
                   site of DCIS (or diagnosis of mass as a cyst). 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
      
                -  Bloody nipple discharge (ipsilateral breast)
      
                -  Mammographic finding of BIRADS 4 or greater within 6 months of registration at site
                   other than that of known DCIS, without pathologic assessment
      
                -  Use of investigational cancer agents within 6 weeks prior to diagnosis
      
                -  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; however, a pregnancy test for all women of
                   child-bearing potential is not mandatory
      
                -  Documented history of prior tamoxifen, aromatase inhibitor, or raloxifene in last 6
                   months
            
      Maximum Eligible Age:99 Years
      Minimum Eligible Age:40 Years
      Eligible Gender:Female
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Proportion of new diagnoses of ipsilateral invasive cancer in GCC and AS arms at 2 years of follow up
      Time Frame:At 2 years follow-up
      Safety Issue:
      Description:To compare the number of patients that develop ipsilateral invasive cancer that received guidance concordant care to the number of patients that were placed on active surveillance after 2 years of follow-up

      Secondary Outcome Measures

      Measure:Quality of Life (QOL)
      Time Frame:Baseline, 6 months, 1 year, and once a year (years 2 through 5)
      Safety Issue:
      Description:Measured by Short Form (SF)-36
      Measure:Psychological outcomes
      Time Frame:Baseline, 6 months, 1 year, and once a year (years 2 through 5)
      Safety Issue:
      Description:Measured by five dimensions questionnaire (EQ-5D)
      Measure:Generalized anxiety
      Time Frame:Baseline, 6 months, 1 year, and once a year (years 2 through 5)
      Safety Issue:
      Description:Measured by the State Trait Anxiety Inventory (STAI) scale
      Measure:Generalized Depression
      Time Frame:Baseline, 6 months, 1 year, and once a year (years 2 through 5)
      Safety Issue:
      Description:Measured by the Center for Epidemiologic Studies Depression Scale (CES-D) 10
      Measure:Coping
      Time Frame:Baseline
      Safety Issue:
      Description:Coping evaluated using the Brief COPE, a shortened form of the COPE Inventory, inclusive of 28 items (14 subscales).
      Measure:Intolerance of uncertainty
      Time Frame:Baseline and at 2 years
      Safety Issue:
      Description:Assessment of feelings of uncertainty using the Intolerance of Uncertainty Scale (Short-form), which has been used in studies of active surveillance in the prostate cancer setting.
      Measure:Mastectomy rate
      Time Frame:2, 5, and 7 year follow-up
      Safety Issue:
      Description:To compare the impact of GCC vs. AS on the number of mastectomies performed in patients with DCIS
      Measure:Breast conservation rate
      Time Frame:2, 5, and 7 year follow-up
      Safety Issue:
      Description:To compare the impact of GCC vs. AS on the number of breast conservation surgeries performed in patients with DCIS
      Measure:Contralateral invasive cancer rate
      Time Frame:2, 5, and 7 year follow-up
      Safety Issue:
      Description:To compare the impact of GCC vs. AS on the rate of development of contralateral invasive cancer in patients with DCIS
      Measure:Overall survival rate
      Time Frame:2, 5, and 7 year follow-up
      Safety Issue:
      Description:To compare the impact of GCC vs. AS on the overall survival rate in patients with DCIS
      Measure:Breast cancer specific survival rate
      Time Frame:2, 5, and 7 year follow-up
      Safety Issue:
      Description:To compare the impact of GCC vs. AS on the breast cancer specific survival rate in patients with DCIS
      Measure:Ipsilateral invasive cancer rate in GCC arm at 5 and 7 year follow-up
      Time Frame:5 and 7 year follow-up
      Safety Issue:
      Description:To determine the number of DCIS patients in the GCC arm that develop ipsilateral invasive cancer
      Measure:Ipsilateral invasive cancer rate in AS arm
      Time Frame:5 and 7 year follow-up
      Safety Issue:
      Description:To determine the number of DCIS patients in the AS arm that develop ipsilateral invasive cancer

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Alliance Foundation Trials, LLC.

      Trial Keywords

      • Ductal Carcinoma

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