Breast CancerPhase 2NCT00496288
Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer
A Phase 2 study testing Prophylactic radiation to the contralateral breast in people with Breast Cancer, run by Assaf-Harofeh Medical Center at 1 site in Israel.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 30 to 90 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Prophylactic radiation to the contralateral breast
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteIsrael
- Study dates
- Mar 2008to Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patient diagnosed with stage I-III breast cancer (AJCC 6), undergoing breast irradiation as part of her adjuvant therapy.
- The patient must be a carrier of a deleterious mutation in BRCA 1/2.
- Age above 30 years.
- 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.
- The patient may be treated with hormonal therapy before, during or after study entry, according to the guidelines of her treating center.
- The patient must have negative gadolinium based MRI of the contralateral breast, no more than 6 months prior to study entry.
Show all 9Show fewer
- The patient refused prophylactic contralateral mastectomy.
- The patient is aware that subsequent breast cancer in the irradiated breast will probably mandate mastectomy.
- The patient consent for contralateral prophylactic irradiation. -
Who cannot join
- Metastatic breast cancer.
- Previous irradiation of the breast or chest wall.
- Pregnancy.
- No concurrent chemotherapy is allowed
- Patients with active connective tissue diseases are excluded due to the potential risk of significant radiotherapy toxicity.
- 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 -
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Assaf-Harofeh Medical Center
Zerrifin, 70300
Ella Evron, MD, 97289778144, alaa@asaf.health.gov.il
Ella Evron, MD
About this study
Official title: Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Prophylactic radiation to the contralateral breast
- Keywords
- BRCA mutation, Breast cancer, Prophylactic breast irradiation, Prevention of contralateral breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prophylactic radiation to the contralateral breastRadiation
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%
| Study group | Role | What they receive |
|---|---|---|
| prophylactic irradiation | Experimental | prophylactic contralateral breast irradiation Receives: Radiation: Prophylactic radiation to the contralateral breast |
| controls | No intervention | Those that do not opt for prophylactic irradiation or mastectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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
Measured: 15 years
Secondary outcomes (2)
Short and long term adverse effects of prophylactic contralateral breast irradiation.
Measured: 15 years
factors that influence patient's choice of treatment
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2007 (estimated)
- Study startMar 2008
- Primary completionMar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assaf-Harofeh Medical Center
- Sponsor type
- Other government
- Collaborators
- Rambam Health Care Campus, Tel-Aviv Sourasky Medical Center, Sheba Medical Center, Soroka University Medical Center, Western Galilee Hospital-Nahariya, Rabin Medical Center
- Investigators
- Ella Evron, MD, Study director, Assaf-Harofeh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00496288
- Sponsor's protocol ID
- 102/07 (HT4351)
- Status last verified
- Jun 2008
- First submitted
- 3 Jul 2007
- Last updated
- 5 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, Harris EE, Gaffney DK, Haffty BG, Dawson LA, Narod SA, Olivotto IA, Eisen A, Whelan TJ, Olopade OI, Isaacs C, Merajver SD, Wong JS, Garber JE, Weber BL. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006 Jun 1;24(16):2437-43. doi: 10.1200/JCO.2005.02.7888. Epub 2006 Apr 24.
PubMed 16636335Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004 Jun 15;22(12):2328-35. doi: 10.1200/JCO.2004.04.033.
PubMed 15197194Evron E, Goldberg H, Ben-David MA, Corn BW. Participation in a Novel Trial Assessing Prophylactic Breast Irradiation: The Importance of Input From the Radiation Oncologist. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):792-794. doi: 10.1016/j.ijrobp.2019.08.004. Epub 2019 Aug 10. No abstract available.
PubMed 31408668Evron E, Ben-David AM, Goldberg H, Fried G, Kaufman B, Catane R, Pfeffer MR, Geffen DB, Chernobelsky P, Karni T, Abdah-Bortnyak R, Rosengarten O, Matceyevsky D, Inbar M, Kuten A, Corn BW. Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer. Ann Oncol. 2019 Mar 1;30(3):412-417. doi: 10.1093/annonc/mdy515.
PubMed 30475942
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer
- ClinicalTrials.gov ID
- NCT00496288
- Acronym / sponsor ID
- 102/07 (HT4351)
- Conditions
- Breast Cancer
- Keywords
- BRCA mutation, Breast cancer, Prophylactic breast irradiation, Prevention of contralateral breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Assaf-Harofeh Medical CenterOther government
- Collaborators
- Rambam Health Care Campus, Tel-Aviv Sourasky Medical Center, Sheba Medical Center, Soroka University Medical Center, Western Galilee Hospital-Nahariya, Rabin Medical Center
- Study start
- Mar 2008
- Primary completion
- Mar 2023 (estimated)
- First posted
- 4 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| prophylactic irradiation | Experimental | Radiation: Prophylactic radiation to the contralateral breastprophylactic contralateral breast irradiation |
| controls | No intervention | –Those that do not opt for prophylactic irradiation or mastectomy |
Who may qualify
- Ages
- 30 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Female patient diagnosed with stage I-III breast cancer (AJCC 6), undergoing breast irradiation as part of her adjuvant therapy.
- The patient must be a carrier of a deleterious mutation in BRCA 1/2.
- Age above 30 years.
- 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.
- The patient may be treated with hormonal therapy before, during or after study entry, according to the guidelines of her treating center.
Key exclusion criteria (6 listed)
- Metastatic breast cancer.
- Previous irradiation of the breast or chest wall.
- Pregnancy.
- No concurrent chemotherapy is allowed
- Patients with active connective tissue diseases are excluded due to the potential risk of significant radiotherapy toxicity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prophylactic radiation to the contralateral breastThe 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% | Radiation | prophylactic irradiation |
Primary outcome
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
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
2 secondary outcomes
Short and long term adverse effects of prophylactic contralateral breast irradiation.
Time frame: 15 years
factors that influence patient's choice of treatment
Time frame: 15 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2011.
- Background: PubMed 16636335Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, Harris EE, Gaffney DK, Haffty BG, Dawson LA, Narod SA, Olivotto IA, Eisen A, Whelan TJ, Olopade OI, Isaacs C, Merajver SD, Wong JS, Garber JE, Weber BL. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006 Jun 1;24(16):2437-43. doi: 10.1200/JCO.2005.02.7888. Epub 2006 Apr 24.
- Background: PubMed 15197194Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004 Jun 15;22(12):2328-35. doi: 10.1200/JCO.2004.04.033.
- Derived from this study: PubMed 31408668Evron E, Goldberg H, Ben-David MA, Corn BW. Participation in a Novel Trial Assessing Prophylactic Breast Irradiation: The Importance of Input From the Radiation Oncologist. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):792-794. doi: 10.1016/j.ijrobp.2019.08.004. Epub 2019 Aug 10. No abstract available.
- Derived from this study: PubMed 30475942Evron E, Ben-David AM, Goldberg H, Fried G, Kaufman B, Catane R, Pfeffer MR, Geffen DB, Chernobelsky P, Karni T, Abdah-Bortnyak R, Rosengarten O, Matceyevsky D, Inbar M, Kuten A, Corn BW. Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer. Ann Oncol. 2019 Mar 1;30(3):412-417. doi: 10.1093/annonc/mdy515.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ella Evron, MD study director
Assaf-Harofeh Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prophylactic radiation to the contralateral breast in people with Breast Cancer, run by Assaf-Harofeh Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ella Evron, MD (972-8-9778144, alaa@asaf.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00496288, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2011.