Back to resultsNipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
Primary Purpose
Breast Cancer, Ductal Carcinoma
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Nipple-Sparing Mastectomy
Breast Reconstruction
Axillary Surgery
Prophylactic Nipple-Areolar Complex RT
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer, Nipple Area Complex, Mastectomy, Radiation Therapy, Nipple-Sparing, Breast Reconstruction
Eligibility Criteria
Inclusion Criteria:
- Patients must have histologically confirmed in-situ or invasive breast carcinoma.
- Tis, T1, T2 invasive or non-invasive carcinoma of the breast; lesion less than 4 cm.
- Unifocal, multifocal or multicentric breast cancers that can be removed by nipple sparing mastectomy with negative surgical margins.
- No extensive intraductal component or patient with distant metastases.
- Patients must be > 18 years of age.
- No concomitant or history of nipple discharge or skin involvement.
- No prior history of malignancy (less than 5 years prior to study entry), except non-melanomatous skin cancer.
- No prior history of radiation to the chest.
- No collagenous disease (systemic lupus erythematosis, scleroderma, dermatomyositis)No previous non-hormonal therapy including radiation or chemotherapy for current breast cancer.
- No patients with Paget's disease of the nipple.
- No patients with co-existing medical conditions with life expectancy < 2 years.
- No pregnant or lactating women.
- Eastern Cooperative Oncology Group (ECOG) 0 - 2.
- Signed study-specific informed consent form prior to the study entry.
Exclusion Criteria:
- Retroareolar breast cancer lesions within one cm, depth from the skin surface.
- Concomitant or history of nipple discharge or skin involvement.
- Patient with distant metastases.
- Patient with extensive intraductal carcinoma.
- Any previously irradiated ipsilateral breast cancer.
- Patients with Paget's disease of the nipple.
- Patients with collagenous diseases, as systemic lupus erythematosis, scleroderma or dermatomyositis.
- Other malignancy, except nonmelanomatous skin cancer, less than 5 years prior to participation in this study.
- Patients who are pregnant or lactating due to potential exposure of the fetus to RT and unknown effects of RT to lactating females.
- Positive surgical margins following nipple sparing mastectomy.
Sites / Locations
- University of Miami Sylvester Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Phase 1 MTD NAC RT
Arm Description
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.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.
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.
Secondary Outcome Measures
Cosmetic Outcome
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
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
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..
Recurrence Rate in Study Participants
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01208974
Brief Title
Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 16, 2010 (Actual)
Primary Completion Date
February 13, 2018 (Actual)
Study Completion Date
May 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Ductal Carcinoma
Keywords
Breast Cancer, Nipple Area Complex, Mastectomy, Radiation Therapy, Nipple-Sparing, Breast Reconstruction
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
Phase 1 dose-escalation/de-escalation.
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 MTD NAC RT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Nipple-Sparing Mastectomy
Other Intervention Name(s)
NAC-sparing mastectomy, Nipple and areola complex-sparing mastectomy
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Breast Reconstruction
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Axillary Surgery
Other Intervention Name(s)
Axillary Dissection, Sentinel Node Biopsy
Intervention Description
Axillary Dissection or Sentinel Node Biopsy (SNB) will be performed at surgeon's discretion.
Intervention Type
Radiation
Intervention Name(s)
Prophylactic Nipple-Areolar Complex RT
Other Intervention Name(s)
Prophylactic NAC Radiation Therapy
Intervention Description
Prophylactic Nipple-Areolar Complex Radiation Therapy per protocol. Administered between weeks 5 to 8.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.
Description
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.
Time Frame
Up to 13 weeks
Secondary Outcome Measure Information:
Title
Cosmetic Outcome
Description
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.
Time Frame
12 months
Title
Disease-Free Survival Rate in Study Participants
Description
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.
Time Frame
Up to 5 years
Title
Overall Survival Rate in Study Participants
Description
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..
Time Frame
Up to 5 years
Title
Recurrence Rate in Study Participants
Description
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.
Time Frame
Up to 5 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have histologically confirmed in-situ or invasive breast carcinoma.
Tis, T1, T2 invasive or non-invasive carcinoma of the breast; lesion less than 4 cm.
Unifocal, multifocal or multicentric breast cancers that can be removed by nipple sparing mastectomy with negative surgical margins.
No extensive intraductal component or patient with distant metastases.
Patients must be > 18 years of age.
No concomitant or history of nipple discharge or skin involvement.
No prior history of malignancy (less than 5 years prior to study entry), except non-melanomatous skin cancer.
No prior history of radiation to the chest.
No collagenous disease (systemic lupus erythematosis, scleroderma, dermatomyositis)No previous non-hormonal therapy including radiation or chemotherapy for current breast cancer.
No patients with Paget's disease of the nipple.
No patients with co-existing medical conditions with life expectancy < 2 years.
No pregnant or lactating women.
Eastern Cooperative Oncology Group (ECOG) 0 - 2.
Signed study-specific informed consent form prior to the study entry.
Exclusion Criteria:
Retroareolar breast cancer lesions within one cm, depth from the skin surface.
Concomitant or history of nipple discharge or skin involvement.
Patient with distant metastases.
Patient with extensive intraductal carcinoma.
Any previously irradiated ipsilateral breast cancer.
Patients with Paget's disease of the nipple.
Patients with collagenous diseases, as systemic lupus erythematosis, scleroderma or dermatomyositis.
Other malignancy, except nonmelanomatous skin cancer, less than 5 years prior to participation in this study.
Patients who are pregnant or lactating due to potential exposure of the fetus to RT and unknown effects of RT to lactating females.
Positive surgical margins following nipple sparing mastectomy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cristiane Takita, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
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