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

• ClinicalTrials.gov Identifier: NCT01208974
• Recruitment Status: Active, not recruiting
• First Posted: September 24, 2010
• Results First Posted: January 18, 2022
• Last Update Posted: January 18, 2022
• Sponsor: University of Miami
• Information provided by (Responsible Party): Cristiane Takita, University of Miami

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Ductal Carcinoma	Procedure: Nipple-Sparing Mastectomy; Procedure: Breast Reconstruction; Procedure: Axillary Surgery; Radiation: Prophylactic Nipple-Areolar Complex RT	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1 dose-escalation/de-escalation.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 16, 2010
• Actual Primary Completion Date: February 13, 2018
• Estimated Study Completion Date: May 2023

Arms and Interventions

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 Name: Prophylactic NAC Radiation Therapy

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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..
4. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

Sponsors and Collaborators

University of Miami

Investigators

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

  Study Documents (Full-Text)

Documents provided by Cristiane Takita, University of Miami:

Study Protocol and Statistical Analysis Plan  [PDF] December 1, 2017

More Information

• Responsible Party: Cristiane Takita, Professor of Clinical, University of Miami
• ClinicalTrials.gov Identifier: NCT01208974
• Other Study ID Numbers: 20090299; SCCC-2009004 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
• First Posted: September 24, 2010
• Results First Posted: January 18, 2022
• Last Update Posted: January 18, 2022
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Cristiane Takita, University of Miami:

Breast Cancer; Nipple Area Complex; Mastectomy; Radiation Therapy; Nipple-Sparing; Breast Reconstruction

Additional relevant MeSH terms:

Breast Neoplasms; Carcinoma, Ductal; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary