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.
Brief Title
Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
DCIS
Ductal Carcinoma in Situ
Eligibility 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)
* 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)
Inclusion 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
* 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
Gender
Female
Gender Based
false
Keywords
Ductal Carcinoma
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
40 Years
NCT Id
NCT02926911
Org Class
Other
Org Full Name
Alliance Foundation Trials, LLC.
Org Study Id
AFT-25
Overall Status
Active, not recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS: A Phase III Prospective Randomized Trial
Primary Outcomes
Outcome Description
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
Outcome Measure
Proportion of New Diagnoses of Ipsilateral Invasive Cancer in Surgery and AM Arms at 2 Years of Follow up
Outcome Time Frame
At 2 years follow-up
Secondary Outcomes
Outcome Description
Measured by Short Form (SF)-36
Outcome Time Frame
Baseline, 6 months, 1 year, and once a year (years 2 through 5)
Outcome Measure
Quality of Life (QOL)
Outcome Description
Measured by five dimensions questionnaire (EQ-5D)
Outcome Time Frame
Baseline, 6 months, 1 year, and once a year (years 2 through 5)
Outcome Measure
Psychological Outcomes
Outcome Description
Measured by the State Trait Anxiety Inventory (STAI) scale
Outcome Time Frame
Baseline, 6 months, 1 year, and once a year (years 2 through 5)
Outcome Measure
Generalized Anxiety
Outcome Description
Measured by the Center for Epidemiologic Studies Depression Scale (CES-D) 10
Outcome Time Frame
Baseline, 6 months, 1 year, and once a year (years 2 through 5)
Outcome Measure
Generalized Depression
Outcome Description
Coping evaluated using the Brief COPE, a shortened form of the COPE Inventory, inclusive of 28 items (14 subscales).
Outcome Time Frame
Baseline
Outcome Measure
Coping
Outcome Description
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.
Outcome Time Frame
Baseline and at 2 years
Outcome Measure
Intolerance of Uncertainty
Outcome Description
To compare the impact of surgery vs. AM on the number of mastectomies performed in patients with DCIS
Outcome Time Frame
2, 5, and 7 year follow-up
Outcome Measure
Mastectomy Rate
Outcome Description
To compare the impact of surgery vs. AM on the number of breast conservation surgeries performed in patients with DCIS
Outcome Time Frame
2, 5, and 7 year follow-up
Outcome Measure
Breast Conservation Rate
Outcome Description
To compare the impact of surgery vs. AM on the rate of development of contralateral invasive cancer in patients with DCIS
Outcome Time Frame
2, 5, and 7 year follow-up
Outcome Measure
Contralateral Invasive Cancer Rate
Outcome Description
To compare the impact of surgery vs. AM on the overall survival rate in patients with DCIS
Outcome Time Frame
2, 5, and 7 year follow-up
Outcome Measure
Overall Survival Rate
Outcome Description
To compare the impact of surgery vs. AM on the breast cancer specific survival rate in patients with DCIS
Outcome Time Frame
2, 5, and 7 year follow-up
Outcome Measure
Breast Cancer Specific Survival Rate
Outcome Description
To determine the number of DCIS patients in the surgery arm that develop ipsilateral invasive cancer
Outcome Time Frame
5 and 7 year follow-up
Outcome Measure
Ipsilateral Invasive Cancer Rate in Surgery Arm at 5 and 7 Year Follow-up
Outcome Description
To determine the number of DCIS patients in the AM arm that develop ipsilateral invasive cancer
Outcome Time Frame
5 and 7 year follow-up
Outcome Measure
Ipsilateral Invasive Cancer Rate in AM Arm
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
40
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sheldon Feldman
Investigator Email
sfeldman@montefiore.org