Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma in Situ

Carcinoma, Ductal

Carcinoma, Intraductal, Noninfiltrating

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Neoplasms

Breast Carcinoma In Situ

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

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

Surgery +/- radiation choice for endocrine therapy

Surgery

Active Monitoring

Shelley Hwang, MD, MPH

Ann Partridge, MD, MPH

Alastair Thompson, MD

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.

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.

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

Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS: A Phase III Prospective Randomized Trial

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.

Determine the rate of use of breast MRI imaging compared to use of other breast imaging techniques

Determine the rate of biopsies performed during follow-up of patients with DCIS

Determine the rate of the performance of radiation therapy on patients with DCIS

Determine the rate of the use of chemotherapy on patients with DCIS

A modified 19-item version of the Breast Cancer Prevention Trial (BCPT) Symptom Checklist will evaluate commonly reported menopausal symptoms

Evaluated with the Brief Pain Inventory, a well-validated general measure of pain and disability worst pain, least pain, and interference

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

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

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).

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

Measured by the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI)

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

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.

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.

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

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

Measured by five dimensions questionnaire (EQ-5D)

Measured by the State Trait Anxiety Inventory (STAI) scale

Measured by the Center for Epidemiologic Studies Depression Scale (CES-D) 10

Coping evaluated using the Brief COPE, a shortened form of the COPE Inventory, inclusive of 28 items (14 subscales).

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.

To compare the impact of surgery vs. AM on the number of mastectomies performed in patients with DCIS

To compare the impact of surgery vs. AM on the number of breast conservation surgeries performed in patients with DCIS

To compare the impact of surgery vs. AM on the rate of development of contralateral invasive cancer in patients with DCIS

To compare the impact of surgery vs. AM on the overall survival rate in patients with DCIS

To compare the impact of surgery vs. AM on the breast cancer specific survival rate in patients with DCIS

To determine the number of DCIS patients in the surgery arm that develop ipsilateral invasive cancer

To determine the number of DCIS patients in the AM arm that develop ipsilateral invasive cancer

Patient-Centered Outcomes Research Institute

Duke University

Dana-Farber Cancer Institute

M.D. Anderson Cancer Center

New York University

Washington University School of Medicine

Alliance Foundation Trials, LLC.

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Docetaxel

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

László Erős

Primary: To determine the pathological remission following the chemotherapy combination docetaxel and doxorubicin in large breast cancer

Secondary:

* Clinical response rate
* To investigate the safety of docetaxel doxorubicin combination in the treatment for neoadjuvant chemotherapy of breast cancer
* Type of surgery (radical/conservative)

Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer

A Multicenter, Open Label, Phase II Trial Evaluating Docetaxel + Anthracycline x 4 Cycles Followed by Docetaxel Single Agent x 4 Cycles as First-Line Therapy in Patients With Her2 Negative Locally Advanced or Metastatic Breast Cancer Who Have Relapsed ≥ 12 Months From Completion of Neoadjuvant/Adjuvant Taxotere®- Based Chemotherapy

Sanofi

Breast Diseases

Skin Diseases

Participants will undergo a Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, if indicated, on Week 1. Anytime between Weeks 5-8, participants will undergo a dose-escalation/de-escalation of prophylactic NAC radiation treatment (RT) twice daily (minimum of 4 hours apart) for 5 days. Dose escalation/de-escalation design are as follows:

* Dose Level I - 10 fractions of 2.0 Gy for a total of 20 Gy
* Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy
* Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy
* Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy

Participants will be treated between cohorts of 2-6 patients per dose level starting at dose level II. Dose escalation stops when 2 out of 2-6 participants encounter Dose Limiting Toxicities (DLT).

Standard of care chemotherapy, at treating physician's discretion, can be initiated 2 weeks after RT.

Subcutaneous Mastectomy (SCM) to be performed, preserving the nipple and areola complex, after a frozen section of the tissue underneath the nipple-areola complex is sampled and found to be negative for tumor. Performed during Week 1.

Nipple-Sparing Mastectomy

Immediate reconstruction of the breast will be performed (after Nipple-Sparing Mastectomy) by the plastic surgeon, type depend on surgeon's discretion and patient's desire. Performed during Week 1.

Breast Reconstruction

Axillary Dissection or Sentinel Node Biopsy (SNB) will be performed at surgeon's discretion.

Axillary Surgery

Prophylactic Nipple-Areolar Complex Radiation Therapy per protocol. Administered between weeks 5 to 8.

Prophylactic Nipple-Areolar Complex RT

Cristiane Takita, MD

The purpose of this research study is to see if a participant's nipple and areola can be safely preserved by adding radiation to these areas after a nipple-sparing mastectomy and immediate breast reconstruction.

Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction

A Phase I Trial Assessing the Safety and Feasibility of Prophylactic Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Immediate Reconstruction in Patients With In-Situ or Invasive Breast Cancer

The recommended Phase II dose will be reported as the MTD at which only 0 or 1 out of 6 participants experiences dose limiting toxicity (DLT). DLT will be reported as any of the following: Grade 4 skin rash or pain, NAC necrosis, any toxicity requiring interruption of NAC irradiation greater than 2 weeks or any grade 4 or 5 treatment related toxicity. Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.

Cosmetic Outcome will be reported as the number of participants in each of the 4 cosmetic outcome category ordinal scale. The 4 cosmetic outcome category scales are excellent, good, fair and poor. Both physician and patient's evaluation will be reported.

Disease-free survival rate in study participants will be assessed. Disease-free survival is defined from the date of surgery until the date of documented recurrence (local or distant) or breast cancer-related death, whichever occurs first. Patients who die without documentation of recurrence will be considered to have had disease recurrence at the time of death, unless there is documented evidence that no recurrence occurred before death.

Overall Survival rate in study participants will be assessed. Overall survival is the defined from the date of surgery until the date of death due to any cause. In the absence of death, follow-up time will be censored by the date of last contact..

Rate of disease recurrence in study participants. The definition of local recurrence is histologic evidence of recurrent carcinoma, either invasive or non-invasive in the nipple-areola complex in the ipsilateral breast. Clinical evidence of carcinoma by physical exam and/or mammograms/MRI will not be evidence of local recurrence until biopsy proof.

University of Miami

Professor of Clinical

Participants who completed Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, and intra-/post-operative period from weeks 1 to 4.

NAC-Sparing Mastectomy

The first 6 participants that had received the starting dose of NAC Prophylactic Radiation Therapy (RT) at Dose Level II - 10 fractions of 2.5 Gy for a total of 25 Gy after completing NAC-Sparing mastectomy.

Prophylactic NAC RT - Dose Level II - 10 Fractions of 2.5 Gy

The second group of 6 participants that had received Prophylactic NAC Radiation Therapy (RT) at Dose Level III - 10 fractions of 3.0 Gy for a total of 30 Gy after completing NAC-Sparing mastectomy, and after the first 6 participants reported 0 dose-limiting toxicities (DLTs) at Dose Level II.

Prophylactic NAC RT - Dose Level III - 10 Fractions of 3.0 Gy

The third group of 6 participants that had received Prophylactic NAC Radiation Therapy (RT) at Dose Level IV - 10 fractions of 3.5 Gy for a total of 35 Gy after completing NAC-Sparing mastectomy, and after the second 6 participants reported 0 dose-limiting toxicities (DLTs) at Dose Level III.

Prophylactic NAC RT - Dose Level IV - 10 Fractions of 3.5 Gy

Phase 1 MTD NAC RT

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Cristiane Takita MD

Participants who received NAC RT after nipple-sparing mastectomy at the following dose levels:

* Dose Level II: 6 participants receiving 10 fractions at 2.5 grays (gy) for total of 25 Gy.
* Dose Level III: 6 participants receiving 10 fractions at 3.0 grays (gy) for total of 30 Gy.
* Dose Level IV: 6 participants receiving 10 fractions at 3.5 grays (gy) for total of 35 Gy.

Prophylactic NAC RT After Nipple-Sparing Mastectomy

A total of 18 participants at dose-escalating study design (6 participants at each dose level - Levels II, III and IV) who received prophylactic NAC RT after nipple-sparing mastectomy were evaluated to assess the MTD/Recommended Phase II dose.

Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.

Cosmetic Outcome

Disease-Free Survival Rate in Study Participants

Overall Survival Rate in Study Participants

Recurrence Rate in Study Participants

Participants who completed Nipple-Areolar Complex (NAC)-sparing mastectomy with immediate reconstruction and axillary surgery, and intra-/post-operative period from weeks 1 to 4. All participants complete this surgery and post-mastectomy period before being assigned to a dosing arm for prophylactic radiation therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS	NCT02926911	DCIS Ductal Carcinom...	Surgery Active Monitori...	40 Years - 99 Years	Alliance Foundation Trials, LLC.
Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer	NCT00461344	Ductal Carcinom...	Docetaxel Doxorubicin	18 Years - 70 Years	Sanofi
Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer	NCT00461344	Ductal Carcinom...	Docetaxel Doxorubicin	18 Years - 70 Years	Sanofi
Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction	NCT01208974	Breast Cancer Ductal Carcinom...	Nipple-Sparing ... Breast Reconstr... Axillary Surger... Prophylactic Ni...	18 Years -	University of Miami
Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS	NCT02926911	DCIS Ductal Carcinom...	Surgery Active Monitori...	40 Years - 99 Years	Alliance Foundation Trials, LLC.

Spots Global Cancer Trial Database for ductal carcinoma