Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2008 by Assaf-Harofeh Medical Center
Sponsor:
Collaborators:
Rambam Health Care Campus
Tel-Aviv Sourasky Medical Center
Sheba Medical Center
Soroka University Medical Center
Western Galilee Hospital-Nahariya
Rabin Medical Center
Information provided by:
Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier:
NCT00496288
First received: July 3, 2007
Last updated: April 4, 2011
Last verified: June 2008
  Purpose

Women with BRCA germline mutations face a very high risk of developing breast cancer during their lives. It was shown that for carrier patients, breast conservation, comprising of lumpectomy followed by whole breast radiation, was not associated with increased risk of ipsilateral breast cancer recurrence as compared with non carriers (10-15% over 10 years), especially if they also underwent prophylactic oophorectomy. Yet their risk of subsequent contralateral breast cancer was significantly increased, reported as high as 25-30% over 10 years and 40% over 15 years, as compared to 3% and 7% respectively in non carriers. The reduction in ipsilateral disease was attributed to radiation of the affected breast. We propose that for breast cancer patients with BRCA germline mutation that choose to have breast-conserving therapy and refuse prophylactic contralateral mastectomy, prophylactic radiation to the contralateral breast may reduce the rate of subsequent contralateral breast cancer and offer an option for risk reduction.


Condition Intervention Phase
Breast Cancer
Radiation: Prophylactic radiation to the contralateral breast
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer

Resource links provided by NLM:


Further study details as provided by Assaf-Harofeh Medical Center:

Primary Outcome Measures:
  • Rate of contralateral breast cancer in carrier patients that received prophylactic radiation to the contralateral breast compared with carrier patients that did not receive that treatment. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
    To compare the rate of contralateral breast cancer in carrier patients that received prophylactic radiation to the contralateral breast to the rate in carrier patients that did not receive that treatment


Secondary Outcome Measures:
  • Short and long term adverse effects of prophylactic contralateral breast irradiation. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  • factors that influence patient's choice of treatment [ Time Frame: 15 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: March 2008
Estimated Primary Completion Date: March 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: prophylactic irradiation
prophylactic contralateral breast irradiation
Radiation: Prophylactic radiation to the contralateral breast
The contralateral breast will be treated with 2 tangent fields, using 1.8-2 Gy/fx to a total dose of 50-50.4 Gy. The whole breast will be treated according to traditional guidelines and as described in the RTOG/NSABP B39 study. The heart should be maximally blocked for left sided breasts, included lung tissue should be reduced to minimum. No overlapping field is allowed on the skin between the two breast fields in the midline. Maximal dose should not exceed 110%
No Intervention: controls
Those that do not opt for prophylactic irradiation or mastectomy

Detailed Description:

Trial design and statistics:

This is a multi center- phase II open comparative trial. "Patients" - Those who choose prophylactic contralateral breast irradiation. "Controls" - Those that do not opt for prophylactic irradiation or mastectomy. Objective - to compare the rate of contralateral breast cancer in "patients" versus "controls".

Assuming that 2/3 of the eligible carrier breast cancer patients refuse the procedure: To detect a difference of 10% vs. 25% in the incidence of contralateral breast cancer with power = 80%, alpha = 0.05, 80 patients and 160 controls need to be enrolled.

Treatment:

Chemotherapy, Hormonal therapy and XRT to the affected breast as per treating institution.

Radiation therapy:

Patients will undergo a pre-treatment planning CT with 5mm cuts in the treatment position, on a breast board, with both arms extended above their head. The organs at risk (heart, lungs) will be contoured on the CT scan.

The affected breast (with the index lesion) and associated lymphatic drainage will be treated according to the treating physician decision. The contralateral breast will be treated with 2 tangent fields, using 1.8-2 Gy/fx to a total dose of 50-50.4 Gy. The whole breast will be treated according to traditional guidelines and as described in the RTOG/NSABP B39 study. The heart should be completely blocked for left sided breasts, included lung tissue should be reduced to minimum. No overlapping field is allowed on the skin between the two breast fields in the midline. Maximal dose should not exceed 110%.

Follow up:

The treating physician will follow the patient every 2 weeks during the radiation treatment. Side effects will be scored and recorded in the patients chart according to the Common Terminology Criteria for Adverse Events v3.0.

Subsequent follow-up schedule according to the treating institution and ASCO guidelines. Patients will undergo annual mammogram and breasts US. Annual breasts MRI and bilateral salpingo-oophorectomy will be recommended.

Ipsilateral and contralateral breast cancer will be recorded and reported. Any subsequent malignancy other than breast cancer will be reported. Long-term radiation side effects will be recorded.

  Eligibility

Ages Eligible for Study:   30 Years to 90 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female patient diagnosed with stage I-III breast cancer (AJCC 6), undergoing breast irradiation as part of her adjuvant therapy.
  2. The patient must be a carrier of a deleterious mutation in BRCA 1/2.
  3. Age above 30 years.
  4. The patient may receive any regimen of adjuvant chemotherapy, according to the treating physician. All cycles of chemotherapy must be completed at least 3 weeks prior to the start of radiation therapy.
  5. The patient may be treated with hormonal therapy before, during or after study entry, according to the guidelines of her treating center.
  6. The patient must have negative gadolinium based MRI of the contralateral breast, no more than 6 months prior to study entry.
  7. The patient refused prophylactic contralateral mastectomy.
  8. The patient is aware that subsequent breast cancer in the irradiated breast will probably mandate mastectomy.
  9. The patient consent for contralateral prophylactic irradiation. -

Exclusion Criteria:

  1. Metastatic breast cancer.
  2. Previous irradiation of the breast or chest wall.
  3. Pregnancy.
  4. No concurrent chemotherapy is allowed
  5. Patients with active connective tissue diseases are excluded due to the potential risk of significant radiotherapy toxicity.
  6. Patients who are unable to lie on their back and raise their arms above their heads in the treatment planning position for radiotherapy are excluded -
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00496288

Contacts
Contact: Ella Evron, MD 972-8-9778144 alaa@asaf.health.gov.il

Locations
Israel
Assaf-Harofeh Medical Center Recruiting
Zerrifin, Israel, 70300
Contact: Ella Evron, MD    97289778144    alaa@asaf.health.gov.il   
Principal Investigator: Ella Evron, MD         
Sponsors and Collaborators
Assaf-Harofeh Medical Center
Rambam Health Care Campus
Tel-Aviv Sourasky Medical Center
Sheba Medical Center
Soroka University Medical Center
Western Galilee Hospital-Nahariya
Rabin Medical Center
Investigators
Study Director: Ella Evron, MD Assaf-Harofeh Medical Center
  More Information

Publications:
Responsible Party: Ella Evron, MD, Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier: NCT00496288     History of Changes
Other Study ID Numbers: 102/07 (HT4351)
Study First Received: July 3, 2007
Last Updated: April 4, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Assaf-Harofeh Medical Center:
BRCA mutation
Breast cancer
Prophylactic breast irradiation
Prevention of contralateral breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 19, 2014