ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01208974
Recruitment Status : Recruiting
First Posted : September 24, 2010
Last Update Posted : March 30, 2018
Sponsor:
Information provided by (Responsible Party):
Cristiane Takita, MD, University of Miami

Brief Summary:

Overall rationale: Prophylactic NAC irradiation after nipple-areola sparing mastectomy and immediate reconstruction for patient with ductal carcinoma in-situ or invasive breast cancer will allow better cosmesis and patient's satisfaction:

  • The use of NAC-sparing mastectomy followed by postoperative NAC (nipple-areola complex) external beam radiotherapy for selected patient with early stage invasive or in-situ breast cancers will be technically feasible and with acceptable complication rates.
  • The cosmetic results after NAC-sparing mastectomy followed by postoperative external beam radiotherapy to the NAC will be better comparable with Skin Sparing Mastectomy.
  • The local control rate in the NAC will be more than expected for a NAC sparing mastectomy without postoperative radiotherapy.
  • The patient's satisfaction after NAC-sparing mastectomy followed by postoperative NAC external beam radiotherapy will be better than after Skin Sparing Mastectomy.

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

Detailed Description:

Study design: Phase I trial assessing the safety, feasibility and toxicity of prophylactic NAC irradiation after nipple-areola sparing mastectomy and immediate reconstruction in patients with ductal carcinoma in-situ or invasive breast cancer.

Primary objective: To determine the recommended phase I dose of post-operative prophylactic NAC irradiation.

Secondary objectives: To provide extensive descriptive data regarding NAC-sparing surgery with reconstruction, including both surgeon experience and patient evaluation of cosmetic results. Survival and recurrence will be assessed.

Study size: Between 12 and 18 patients will be enrolled in the dose-escalation/deescalation part of this phase I study. An additional expansion cohort of 12 patients will be enrolled at the "potential" recommended phase II dose (RP2D) over an expected accrual period of 2 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1 dose-escalation/de-escalation. An additional expansion cohort at the "potential" recommended Phase 2 dose
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
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 MTD NAC RT

Phase 1 dose-escalation/de-escalation Prophylactic Nipple-Areolar Complex (NAC) radiation therapy (RT) to determine the maximum tolerated dose (MTD).

  • Nipple-Sparing Mastectomy
  • Axillary surgery
  • Immediate Breast Reconstruction
  • Prophylactic Nipple-Areolar Complex RT at one of the following four possible dose levels:

    • Dose level I: 20 Gy total (2.0 Gy for 10 fractions)
    • Dose level II: 25 Gy total (2.5 Gy for 10 fractions) (Starting Dose)
    • Dose level III: 30 Gy total (3.0 Gy for 10 fractions)
    • Dose level IV: 35 Gy total (3.5 Gy for 10 fractions)
  • Chemotherapy, if indicated, at physician discretion
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

Experimental: Potential RP2D Expansion

"Potential" recommended phase 2 dose (RP2D) expansion cohort:

  • Nipple-Sparing Mastectomy
  • Axillary surgery
  • Immediate Breast Reconstruction
  • Prophylactic Nipple-Areolar Complex RT at the potential RP2D
  • Chemotherapy, if indicated, at physician discretion
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




Primary Outcome Measures :
  1. Determination of the Recommended Phase II Dose (RP2D) of post-operative prophylactic NAC irradiation. [ Time Frame: 3-5 Years ]
    The recommended phase II dose will be the highest irradiation dose level at which <= 1 out of 6 study patients experiences dose-limiting toxicity (DLT). This dose will be the phase dose II of post-operative prophylactic NAC irradiation after NAC-sparing mastectomy with reconstruction in patients with ductal carcinoma in-situ or invasive breast cancer.


Secondary Outcome Measures :
  1. Surgery Success Rate [ Time Frame: Up to 12 months ]
    Surgery success rate, defined as the proportion of patients who had successful NAC sparing surgery with reconstruction divided by the total number of study patients, will be determined.

  2. Levels of Cosmetic Outcome in Study Participants - Number [ Time Frame: 3, 6 and 12 months ]
    Levels of cosmetic results will be assessed by both the physician(s) and the patients at 3, 6 and 12 months, using a 4-category ordinal scale (excellent, good, fair, and poor). Data will be summarized in terms of number of patients in these 4 possible categories at those assessment times separately for assessment by physician and by patient.

  3. Levels of Cosmetic Outcome in Study Participants - Percentage [ Time Frame: 3, 6 and 12 months ]
    Levels of cosmetic results will be assessed by both the physician(s) and the patients at 3, 6 and 12 months, using a 4-category ordinal scale (excellent, good, fair, and poor). Data will be summarized in terms of percentage of patients in these 4 possible categories at those assessment times separately for assessment by physician and by patient.

  4. 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.

  5. 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..

  6. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01208974


Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Cristiane Takita, MD       ctakita@med.miami.edu   
Principal Investigator: Eli Avisar, MD         
Principal Investigator: Cristiane Takita, MD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Cristiane Takita, MD University of Miami

Responsible Party: Cristiane Takita, MD, Professor of Clinical, University of Miami
ClinicalTrials.gov Identifier: NCT01208974     History of Changes
Other Study ID Numbers: 20090299
SCCC-2009004 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
First Posted: September 24, 2010    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018

Keywords provided by Cristiane Takita, MD, 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