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

May 1, 2023 updated by: Cristiane Takita, University of Miami

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 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 MTD NAC RT

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.
Procedure: Nipple-Sparing Mastectomy
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.
Other Names:
  • NAC-sparing mastectomy
  • Nipple and areola complex-sparing mastectomy
Procedure: Breast Reconstruction
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.
Procedure: Axillary Surgery
Axillary Dissection or Sentinel Node Biopsy (SNB) will be performed at surgeon's discretion.
Other Names:
  • Axillary Dissection
  • Sentinel Node Biopsy
Radiation: Prophylactic Nipple-Areolar Complex RT
Prophylactic Nipple-Areolar Complex Radiation Therapy per protocol. Administered between weeks 5 to 8.
Other Names:
  • Prophylactic NAC Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Prophylactic NAC Irradiation.
Time Frame: Up to 13 weeks
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.
Up to 13 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cosmetic Outcome
Time Frame: 12 months
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.
12 months
Disease-Free Survival Rate in Study Participants
Time Frame: Up to 5 years
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.
Up to 5 years
Overall Survival Rate in Study Participants
Time Frame: Up to 5 years
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..
Up to 5 years
Recurrence Rate in Study Participants
Time Frame: Up to 5 years
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.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Investigators

  • Principal Investigator: Cristiane Takita, MD, University of Miami

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 16, 2010

Primary Completion (Actual)

February 13, 2018

Study Completion (Anticipated)

May 31, 2024

Study Registration Dates

First Submitted

September 22, 2010

First Submitted That Met QC Criteria

September 23, 2010

First Posted (Estimate)

September 24, 2010

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

May 1, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20090299
  • SCCC-2009004 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Nipple-Sparing Mastectomy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Algeria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe