Surgery vs Active Monitoring for Low-Risk Ductal Carcinoma In Situ

(COMET Trial)

Recruiting at 138 trial locations

Overseen By Nancy DeMore, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: Tamoxifen, Aromatase inhibitors, Raloxifene, Hormones

Disqualifiers: Male DCIS, Grade III DCIS, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 5 years

997 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have used certain hormone therapies like tamoxifen, aromatase inhibitors, or raloxifene in the past 6 months, and those currently using exogenous hormones like oral progesterone.

What data supports the effectiveness of the treatment Active Monitoring for Low-Risk Ductal Carcinoma In Situ?

Observational studies suggest that active monitoring can have similar outcomes to immediate treatment for certain patients with low-risk ductal carcinoma in situ, meaning it might be a safe option for some individuals. ^{1 2 3 4 5}

Is active monitoring safe for low-risk ductal carcinoma in situ (DCIS)?

While specific safety data from clinical trials is not yet available, observational studies suggest that active monitoring for low-risk ductal carcinoma in situ (DCIS) shows similar outcomes to immediate treatment in certain patient groups, indicating it may be a safe option. ^{3 5 6 7 8}

How does the treatment of active monitoring differ from surgery for low-risk ductal carcinoma in situ?

Active monitoring involves regular check-ups and assessments to track the condition without immediate surgery, which can help avoid unnecessary procedures and their associated risks and costs. This approach is similar to how low-risk papillary thyroid microcarcinoma is managed, where active surveillance has shown to be effective in identifying patients who may eventually need surgery, while minimizing adverse events and medical expenses. ^{9 10 11 12 13}

What is the purpose of this trial?

This trial compares regular check-ups to surgery for women with low-risk Ductal Carcinoma in Situ (DCIS). The goal is to see if monitoring the condition without immediate surgery can provide similar outcomes in terms of cancer control and quality of life. Surgery can lead to persistent pain and other issues, so avoiding it might benefit patients. The study is examining the safety of monitoring low-risk DCIS without surgery.

Research Team

Shelley Hwang, MD

Principal Investigator

Duke University

Ann Partridge, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Alastair Thompson, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for women aged 40 or older diagnosed with low-risk DCIS (a type of breast condition) who haven't had previous breast cancer in the same breast within 5 years. Participants should be able to undergo surgery if needed, have a good performance status, and agree to regular follow-ups. Pregnant women, those with certain serious conditions, or prior use of specific hormone treatments are excluded.

Inclusion Criteria

I have been diagnosed with a type of non-invasive breast cancer.

Baseline imaging requirements met

Amenable to follow-up examinations

Exclusion Criteria

I have colored or bloody discharge from the nipple on one side.

I have taken tamoxifen, an aromatase inhibitor, or raloxifene in the last 6 months.

I had a lump found by exam or imaging before being diagnosed with DCIS.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either active monitoring or surgery with optional endocrine therapy

5 years

MMG every 6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Annual follow-up visits

Treatment Details

Interventions

• Active Monitoring
• Surgery

Trial Overview The COMET Trial is comparing active monitoring versus surgery for managing low-risk Ductal Carcinoma In Situ (DCIS). The study aims to determine whether active monitoring leads to similar cancer outcomes and quality of life as compared to surgical intervention.

Participant Groups

Group I: Active Monitoring Experimental Treatment 1 Intervention

DCIS - Choice for endocrine therapy (MMG q 6 months x 5 years GCC for invasive progression)

Group II: Surgery Active Control 1 Intervention

DCIS - Surgery +/- radiation choice for endocrine therapy (MMG q 12 months x 5 years usual care for recurrent disease)

Active Monitoring is already approved in Canada for the following indications:

Approved in Canada as Active Monitoring for:

• Posttraumatic Stress Injuries (PTSI)
• Mental Health Risk and Resilience Factors

Who Is Running the Clinical Trial?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

The University of Texas MD Anderson Cancer Center

Collaborator

Trials

2

Recruited

1,100+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

New York University

Collaborator

Trials

249

Recruited

229,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Findings from Research

In a study of 37,544 women with a clinical diagnosis of non-high-grade ductal carcinoma in situ (DCIS), 22.2% were found to have invasive carcinoma upon final pathologic examination, highlighting the risk of underestimating invasive cancer in these patients.

Factors such as younger age, negative estrogen receptor status, treatment at academic facilities, and higher income were significantly associated with an upgraded diagnosis of invasive carcinoma, suggesting that these should be considered when deciding on active surveillance for DCIS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Underestimation of Invasive Cancer in Patients With Ductal Carcinoma In Situ: Precautions for Active Surveillance. Chavez de Paz Villanueva, C., Bonev, V., Senthil, M., et al.[2022]

In a study of 14,419 women treated for ductal carcinoma in situ (DCIS) in the Netherlands, those who underwent breast-conserving surgery (BCS) alone had a higher risk of developing ipsilateral invasive breast cancer (iIBC) compared to those who received BCS plus radiotherapy (RT), with a cumulative incidence of 7.1% versus 3.1% after 10 years.

The risk of iIBC remained significantly elevated in the BCS alone group for at least 10 years post-treatment, indicating that adding radiotherapy after BCS may provide a protective effect against the development of invasive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population. Alaeikhanehshir, S., Schmitz, RSJM., van den Belt-Dusebout, AW., et al.[2023]

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) showed similar oncological outcomes to immediate surgery (IS) in a study of 816 patients, suggesting it is a viable treatment option.

Patients undergoing IS experienced significantly higher rates of temporary vocal cord paralysis and hypoparathyroidism, along with more complaints about quality of life related to voice and scarring, indicating that AS may offer a safer alternative with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China. Liu, C., Zhao, H., Xia, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Factors Associated With Underestimation of Invasive Cancer in Patients With Ductal Carcinoma In Situ: Precautions for Active Surveillance. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Surgical upstaging rates in patients meeting the eligibility for active surveillance trials. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A web-based personalized decision support tool for patients diagnosed with ductal carcinoma in situ: development, content evaluation, and usability testing. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Follow-up for screen-detected ductal carcinoma in situ: results of a survey of UK centres participating in the Sloane project. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treating (low-risk) DCIS patients: What can we learn from real-world cancer registry evidence? [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Symptomatic ductal carcinoma in situ (DCIS): Upstaging risk and predictors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Long-term oncologic outcomes of papillary thyroid microcarcinoma according to the presence of clinically apparent lymph node metastasis: a large retrospective analysis of 5,348 patients. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Conservative Surveillance Management of Low-Risk Papillary Thyroid Microcarcinoma. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

The safety and efficacy of delayed surgery by simulating clinical progression of observable papillary thyroid microcarcinoma: a retrospective analysis of 524 patients from a single medical center. [2023]

13. Japan pubmed.ncbi.nlm.nih.gov

Active surveillance is an excellent management technique for identifying patients with progressive low-risk papillary thyroid microcarcinoma requiring surgical treatment. [2023]