Breast CancerPhase 3NCT02104895
Accelerated Partial Breast Irradiation Using Intensity Modulated Radiotherapy Versus Whole Breast Irradiation
A Phase 3 study testing Accelerated partial breast irradiation (APBI) and Whole breast irradiation (WBI) in people with Breast Cancer, run by Azienda Ospedaliero-Universitaria Careggi.
Trial summary
The aim of this Phase 3 randomised trial is to compare the efficacy and safety of whole breast radiotherapy to accelerated partial breast irradiation using intensity-modulated radiotherapy technique in selected early breast cancer patients after breast conserving surgery. Read more about this study
- Who is it for?
- Ages 40 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Accelerated partial breast irradiation (APBI) and Whole breast irradiation (WBI)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 520 participants
- Where
- No sites listed yet
- Study dates
- Mar 2005to Feb 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age at presentation >40 y
- Tumor size <25 mm
- Wide excision or quadrantectomy with clear margins (>5 mm)
- Clips placed in tumor bed
- Full informed consent from patient
Who cannot join
- Cardiac dysfunction
- Forced expiratory volume in 1 second (FEV1) <1 L/m
- Extensive intraductal carcinoma
- Multifocal cancer
- Psychiatric problems
- Recurrent breast cancer
About this study
Official title: Randomised Phase 3 Trial Of Accelerated Partial Breast Irradiation Using Intensity Modulated Radiotherapy Versus Whole Breast Irradiation
The aim of this Phase 3 randomised trial is to compare the efficacy and safety of whole breast radiotherapy to accelerated partial breast irradiation using intensity-modulated radiotherapy technique in selected early breast cancer patients after breast conserving surgery.
Read the detailed description
The surgeons were requested to place clips at the borders of the surgical bed, using a minimum of four clips. The presence of surgical clips was a selection criterion to avoid geographic misses. Computed tomography (CT) scanning was performed using 0.3-cm thick-slices and a slice spacing of 0.3 cm.
In patients assigned to APBI arm, the clinical target volume (CTV) was drawn with a uniform 1-cm three-dimensional margin around the surgical clips. The CTV was limited to 3 mm from the skin surface and 3 mm from the lung-chest wall interface. A second uniform, three-dimensional 1-cm margin was added to the CTV to obtain the planning target volume (PTV). The PTV was allowed to extend 4 mm inside the ipsilateral lung and was limited to 3 mm from the skin. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk.
All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. No respiratory control was used.
Concerning the experimental Arm (accelerated partial breast irradiation), a dose of 30 Gy in five fractions at 6 Gy/fraction was prescribed.
The following constraints were adopted for plan optimization: PTV coverage: 100% of PTV covered by 95% of the prescribed dose (V28.5 = 100%); maximal dose to PTV <105% (31.5 Gy); minimal dose to PTV 28 Gy; uninvolved breast (i.e., ipsilateral breast without PTV): not >50% covered by a dose of >50% of the prescribed dose (V15 <50%); ipsilateral lung: not >20% covered by a dose >10 Gy (V10<20%); contralateral lung: not >10% covered by a dose >5 Gy (V5<10%); contralateral breast: maximal dose <1 Gy; heart: not >10% covered by a dose >3 Gy (V3 <10%).
- Conditions
- Breast Cancer
- Being tested
- Accelerated partial breast irradiation (APBI), Whole breast irradiation (WBI)
- Keywords
- Breast cancer, Early breast cancer, Adjuvant breast cancer, Accelerated partial breast irradiation, Intensity modulated radiotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Accelerated partial breast irradiation (APBI)Radiation
Accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT)
Whole breast irradiation (WBI)Radiation
Conventional whole breast irradiation (WBI)
| Study group | Role | What they receive |
|---|---|---|
| Whole breast irradiation (WBI) | Active comparator | Conventional whole breast irradiation (WBI) Receives: Radiation: Whole breast irradiation (WBI) |
| Partial breast irradiation (APBI) | Experimental | Accelerated partial breast irradiation (APBI) Receives: Radiation: Accelerated partial breast irradiation (APBI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ipsilateral Breast Tumor Recurrence
We defined local relapse (true recurrence) as the reappearance of the breast cancer in the index quadrant and ipsilateral breast tumours as any new breast cancer diagnosed in other quadrants of the same breast. The sum of local relapses and new ipsilateral breast tumours was defined as the ipsilateral breast tumour recurrence (IBTR). Locoregional tumour recurrence also included any recurrence in the ipsilateral axillary, supraclavicular, or internal mammary chain nodal regions.here we report the percentage of participants in each arm who experienced "Ipsilateral Breast Tumor Recurrence"
Measured: 5-year
Secondary outcomes (2)
Acute Skin Toxicity
Acute skin toxicity ≥ grade 2, here we report the percentage of participants in each arm who experienced "Acute skin toxicity ≥ grade 2
Measured: 5 years
Excellent Cosmesis
Physician-rated cosmesis, Cosmetic outcome was scored on the four-category Harvard Breast Cosmesis Scale. An excellent cosmetic result score was assigned when the treated breast looked like the contralateral one; a good cosmetic score was assigned for minimal but identifiable radiation effects of the treated breast; a fair score was used if significant radiation effects were readily observable; a poor score was used for severe sequelae due to radiation effects
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study startMar 2005
- Primary completionJun 2013
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 520 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria Careggi
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Livi, Azienda Ospedaliero-Universitaria Careggi
- Investigators
- Lorenzo Livi, Full Prof, Principal investigator, Florence UniversityIcro Meattini, M.D., Principal investigator, Azienda Ospedaliero-Universitaria Careggi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02104895
- Sponsor's protocol ID
- APBI-IMRT-Florence
- Status last verified
- Jul 2016
- First submitted
- 2 Apr 2014
- Last updated
- 11 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Livi L, Buonamici FB, Simontacchi G, Scotti V, Fambrini M, Compagnucci A, Paiar F, Scoccianti S, Pallotta S, Detti B, Agresti B, Talamonti C, Mangoni M, Bianchi S, Cataliotti L, Marrazzo L, Bucciolini M, Biti G. Accelerated partial breast irradiation with IMRT: new technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):509-15. doi: 10.1016/j.ijrobp.2009.04.070. Epub 2009 Aug 21.
PubMed 19700248Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, Paiar F, Scotti V, De Luca Cardillo C, Bastiani P, Orzalesi L, Casella D, Sanchez L, Nori J, Fambrini M, Bianchi S. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015 Mar;51(4):451-463. doi: 10.1016/j.ejca.2014.12.013. Epub 2015 Jan 17.
PubMed 25605582Meattini I, Saieva C, Marrazzo L, Di Brina L, Pallotta S, Mangoni M, Meacci F, Bendinelli B, Francolini G, Desideri I, De Luca Cardillo C, Scotti V, Furfaro IF, Rossi F, Greto D, Bonomo P, Casella D, Bernini M, Sanchez L, Orzalesi L, Simoncini R, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial. Breast Cancer Res Treat. 2015 Oct;153(3):539-47. doi: 10.1007/s10549-015-3565-2. Epub 2015 Sep 9.
PubMed 26350524Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, Bonomo P, Greto D, Mangoni M, Scoccianti S, Lucidi S, Paoletti L, Fambrini M, Bernini M, Sanchez L, Orzalesi L, Nori J, Bianchi S, Pallotta S, Livi L. Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020 Dec 10;38(35):4175-4183. doi: 10.1200/JCO.20.00650. Epub 2020 Aug 24.
PubMed 32840419Becherini C, Meattini I, Livi L, Garlatti P, Desideri I, Scotti V, Orzalesi L, Sanchez LJ, Bernini M, Casella D, Nesi S, Nori J, Bianchi S, Pallotta S, Marrazzo L. External accelerated partial breast irradiation for ductal carcinoma in situ: long-term follow-up from a phase 3 randomized trial. Tumori. 2019 Jun;105(3):205-209. doi: 10.1177/0300891618811278. Epub 2018 Nov 26.
PubMed 30474504Meattini I, Saieva C, Miccinesi G, Desideri I, Francolini G, Scotti V, Marrazzo L, Pallotta S, Meacci F, Muntoni C, Bendinelli B, Sanchez LJ, Bernini M, Orzalesi L, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial. Eur J Cancer. 2017 May;76:17-26. doi: 10.1016/j.ejca.2017.01.023. Epub 2017 Mar 3.
PubMed 28262584
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Phase 3 Trial Of Accelerated Partial Breast Irradiation Using Intensity Modulated Radiotherapy Versus Whole Breast Irradiation
- ClinicalTrials.gov ID
- NCT02104895
- Acronym / sponsor ID
- APBI-IMRT-Florence
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Early breast cancer, Adjuvant breast cancer, Accelerated partial breast irradiation, Intensity modulated radiotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 520 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria CareggiUniversity, hospital or other
- Study start
- Mar 2005
- Primary completion
- Jun 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 7 Apr 2014 (estimated)
- Results
- Posted 11 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this Phase 3 randomised trial is to compare the efficacy and safety of whole breast radiotherapy to accelerated partial breast irradiation using intensity-modulated radiotherapy technique in selected early breast cancer patients after breast conserving surgery.
Detailed description
The surgeons were requested to place clips at the borders of the surgical bed, using a minimum of four clips. The presence of surgical clips was a selection criterion to avoid geographic misses. Computed tomography (CT) scanning was performed using 0.3-cm thick-slices and a slice spacing of 0.3 cm.
In patients assigned to APBI arm, the clinical target volume (CTV) was drawn with a uniform 1-cm three-dimensional margin around the surgical clips. The CTV was limited to 3 mm from the skin surface and 3 mm from the lung-chest wall interface. A second uniform, three-dimensional 1-cm margin was added to the CTV to obtain the planning target volume (PTV). The PTV was allowed to extend 4 mm inside the ipsilateral lung and was limited to 3 mm from the skin. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk.
All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. No respiratory control was used.
Concerning the experimental Arm (accelerated partial breast irradiation), a dose of 30 Gy in five fractions at 6 Gy/fraction was prescribed.
The following constraints were adopted for plan optimization: PTV coverage: 100% of PTV covered by 95% of the prescribed dose (V28.5 = 100%); maximal dose to PTV <105% (31.5 Gy); minimal dose to PTV 28 Gy; uninvolved breast (i.e., ipsilateral breast without PTV): not >50% covered by a dose of >50% of the prescribed dose (V15 <50%); ipsilateral lung: not >20% covered by a dose >10 Gy (V10<20%); contralateral lung: not >10% covered by a dose >5 Gy (V5<10%); contralateral breast: maximal dose <1 Gy; heart: not >10% covered by a dose >3 Gy (V3 <10%).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Whole breast irradiation (WBI) | Active comparator | Radiation: Whole breast irradiation (WBI)Conventional whole breast irradiation (WBI) |
| Partial breast irradiation (APBI) | Experimental | Radiation: Accelerated partial breast irradiation (APBI)Accelerated partial breast irradiation (APBI) |
Who may qualify
- Ages
- 40 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age at presentation >40 y
- Tumor size <25 mm
- Wide excision or quadrantectomy with clear margins (>5 mm)
- Clips placed in tumor bed
- Full informed consent from patient
Key exclusion criteria (6 listed)
- Cardiac dysfunction
- Forced expiratory volume in 1 second (FEV1) <1 L/m
- Extensive intraductal carcinoma
- Multifocal cancer
- Psychiatric problems
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 |
|---|---|---|
| Accelerated partial breast irradiation (APBI)Accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT) | Radiation | Partial breast irradiation (APBI) |
| Whole breast irradiation (WBI)Conventional whole breast irradiation (WBI) | Radiation | Whole breast irradiation (WBI) |
Primary outcome
Ipsilateral Breast Tumor Recurrence
Time frame: 5-year
We defined local relapse (true recurrence) as the reappearance of the breast cancer in the index quadrant and ipsilateral breast tumours as any new breast cancer diagnosed in other quadrants of the same breast. The sum of local relapses and new ipsilateral breast tumours was defined as the ipsilateral breast tumour recurrence (IBTR). Locoregional tumour recurrence also included any recurrence in the ipsilateral axillary, supraclavicular, or internal mammary chain nodal regions.here we report the percentage of participants in each arm who experienced "Ipsilateral Breast Tumor Recurrence"
2 secondary outcomes
Acute Skin Toxicity
Time frame: 5 years
Excellent Cosmesis
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19700248Livi L, Buonamici FB, Simontacchi G, Scotti V, Fambrini M, Compagnucci A, Paiar F, Scoccianti S, Pallotta S, Detti B, Agresti B, Talamonti C, Mangoni M, Bianchi S, Cataliotti L, Marrazzo L, Bucciolini M, Biti G. Accelerated partial breast irradiation with IMRT: new technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):509-15. doi: 10.1016/j.ijrobp.2009.04.070. Epub 2009 Aug 21.
- Results publication: PubMed 25605582Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, Paiar F, Scotti V, De Luca Cardillo C, Bastiani P, Orzalesi L, Casella D, Sanchez L, Nori J, Fambrini M, Bianchi S. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015 Mar;51(4):451-463. doi: 10.1016/j.ejca.2014.12.013. Epub 2015 Jan 17.
- Results publication: PubMed 26350524Meattini I, Saieva C, Marrazzo L, Di Brina L, Pallotta S, Mangoni M, Meacci F, Bendinelli B, Francolini G, Desideri I, De Luca Cardillo C, Scotti V, Furfaro IF, Rossi F, Greto D, Bonomo P, Casella D, Bernini M, Sanchez L, Orzalesi L, Simoncini R, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial. Breast Cancer Res Treat. 2015 Oct;153(3):539-47. doi: 10.1007/s10549-015-3565-2. Epub 2015 Sep 9.
- Derived from this study: PubMed 32840419Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, Bonomo P, Greto D, Mangoni M, Scoccianti S, Lucidi S, Paoletti L, Fambrini M, Bernini M, Sanchez L, Orzalesi L, Nori J, Bianchi S, Pallotta S, Livi L. Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020 Dec 10;38(35):4175-4183. doi: 10.1200/JCO.20.00650. Epub 2020 Aug 24.
- Derived from this study: PubMed 30474504Becherini C, Meattini I, Livi L, Garlatti P, Desideri I, Scotti V, Orzalesi L, Sanchez LJ, Bernini M, Casella D, Nesi S, Nori J, Bianchi S, Pallotta S, Marrazzo L. External accelerated partial breast irradiation for ductal carcinoma in situ: long-term follow-up from a phase 3 randomized trial. Tumori. 2019 Jun;105(3):205-209. doi: 10.1177/0300891618811278. Epub 2018 Nov 26.
- Derived from this study: PubMed 28262584Meattini I, Saieva C, Miccinesi G, Desideri I, Francolini G, Scotti V, Marrazzo L, Pallotta S, Meacci F, Muntoni C, Bendinelli B, Sanchez LJ, Bernini M, Orzalesi L, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial. Eur J Cancer. 2017 May;76:17-26. doi: 10.1016/j.ejca.2017.01.023. Epub 2017 Mar 3.
- Individual participant dataSharing planned: Undecided
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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.
Lorenzo Livi, Full Prof principal investigator
Florence University
Icro Meattini, M.D. principal investigator
Azienda Ospedaliero-Universitaria Careggi
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Accelerated partial breast irradiation (APBI) and Whole breast irradiation (WBI) in people with Breast Cancer, run by Azienda Ospedaliero-Universitaria Careggi.
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 5 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: finished, as of the sponsor's last update on 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ipsilateral Breast Tumor Recurrence (time frame: 5-year). 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 NCT02104895, which also lists 6 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 11 Aug 2016.