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

  • Interventional
  • Recruiting
  • NCT02926911
Eligibility Details Visit Clinicaltrials.gov

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

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.

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).

Gender
Female

Age Group
40 Years to 99 Years

Accepting Healthy Volunteers?
No

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

At a Glance

National Government IDNCT02926911

IRB#IRB17-0777

Lead SponsorAlliance Foundation Trials, LLC.

Lead PhysicianJean Bao

Collaborator(s)N/A

EligibilityFemale
40 Years to 99 Years
Recruiting