Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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.

Spots Global Cancer Trial Database for Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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