Breast CancerACCELNCT02681107
APBI: 27Gy in 5 Fractions for Early Breast Cancer
A study testing APBI 27Gy in 5 fractions in people with Breast Cancer, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial summary
This study will test the safety of partial breast RT using 27Gy in 5 daily fractions which is expected to be equally tolerated as standard whole breast irradiation (WBI) based on radiobiologic modeling of the fibrosis response of normal tissues but be more convenient and less costly than 3-6 weeks of standard WBI. Read more about this study
- Who is it for?
- Ages 50 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- APBI 27Gy in 5 fractions
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 274 participants
- Where
- 1 siteCanada
- Study dates
- May 2016to Jul 2021
- Phase
- Interventional
- 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 50 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female, with new invasive or in-situ ductal carcinoma of the breast
- Treated with Breast conserving surgery (BCS) with negative margins
- pN0 on sentinel node biopsy or axillary dissection; cN0 if DCIS alone
- Maximum pathologic tumor diameter is 3.0 cm (invasive or DCIS)
- No clinical or imaging evidence of distant metastases
- Age 50 years or older at diagnosis
Show all 10Show fewer
- No contraindications to breast irradiation
- Excellent or Good overall cosmetic score at baseline following BCS
- Able and willing to provide written informed consent
- Available for 2 year follow up at the treating RT centre
Who cannot join
- Age < 50 years at diagnosis
- BRCA 1 or 2 pathogenic mutation
- Pathologic tumor diameter >3cm (including DCIS+invasive disease)
- Lobular histology alone
- Triple negative (ER-, PR-, HER2-) or HER2 overexpressing disease
- Margin (other than deep) <2 mm
Show all 13Show fewer
- Presence of both Grade 3 and lymphatic or vascular invasion
- Fair or Poor overall cosmetic score at baseline following BCS
- Presence of ipsilateral breast implants
- Inability to develop an APBI plan meeting all dosimetry constraints
- Unable to start RT within 16 weeks of BCS or 8 weeks of last iv chemotherapy
- Unable or unwilling to sign informed consent document or attend for 2-year cosmetic assessment at the treating RT centre
- Potential contraindications for breast RT including a confirmed diagnosis of lupus, scleroderma, or pregnancy
Trial locations and contacts
1 site in 1 country.
Mark Lesiuk, BSc contact
Canada1 site, 1 recruiting
- Recruiting
Tom Baker Cancer Centre
Calgary, Alberta
Mark Lesiuk, BScRT MRTT, 403-521-3958, Mark.Lesiuk@albertahealthservices.ca
About this study
Official title: Accelerated Partial Breast Irradiation Using Five Daily Fractions: A Single Arm, Phase II, Prospective Cohort Study to Examine Cosmetic Outcomes and Toxicity (The ACCEL Trial)
This study will test the safety of partial breast RT using 27Gy in 5 daily fractions which is expected to be equally tolerated as standard whole breast irradiation (WBI) based on radiobiologic modeling of the fibrosis response of normal tissues but be more convenient and less costly than 3-6 weeks of standard WBI. 274 women will be treated. Rates of fibrosis and cosmesis at 2 years will be compared to data already collected using standard WBI in the Canadian RAPID trial.
Read the detailed description
Background: Previously, accelerated partial breast irradiation (APBI) using 3D conformal external beam techniques to deliver 38.5Gy in 10, twice daily, fractions caused worse fibrosis and cosmetic deterioration than standard whole breast irradiation (WBI) following breast conserving surgery (BCS) for women with early breast cancer. Over the decade since the original APBI technique was designed, long-term outcomes of various breast RT fractionation regimens have become available and suggest that normal tissue fibrosis and cosmesis varies with the radiobiological constant: α/β=2 rather than α/β=3.4 as previously estimated. Radiobiologic modeling using α/β=2, indicates that a dose of 27Gy in 5 daily treatments should result in comparable late effects as 42.5Gy in 16, or 50Gy in 25 fractions. This clinical trial will validate the safety of a short, convenient and less costly APBI using 27Gy in 5 daily fractions.
Objective: To determine the cosmetic and normal tissue outcomes of APBI using 3D-conformal RT with 27Gy in 5 fractions over 1 week.
Methods: A single-arm, phase II, non-inferiority, prospective study will be conducted. 274 women with newly diagnosed, invasive or in-situ ductal carcinoma treated with BCS and sentinel lymph node biopsy (or axillary dissection) who are candidates for WBI alone, will be treated. Subjects will be age 50 years and older, with tumors less than 3cm diameter, with negative margins and nodes and with excellent or good baseline cosmetic outcome following BCS. Patients with extensive ductal carcinoma in-situ, BRCA mutations, Grade 3 cancers with lymphatic or vascular invasion, or lobular carcinoma will be excluded. These selection criteria are similar to the Canadian RAPID trial. In the first phase of the study, 150 patients will be recruited and interim analyses will be conducted to rule out unacceptable toxicity at 2 years.
Study endpoints: The primary endpoint will be the proportion of women who retain an Excellent or Good cosmetic score at 2 years using the EORTC Cosmetic Rating System and clinical photographs taken prior to, and at 1 and 2 years after RT. Secondary endpoints will include rates and grades of breast fibrosis, induration, telangiectasia, breast pain, ipsilateral breast tumor recurrence, overall and breast cancer-specific survival and subsequent mastectomy rates.
Sample size, statistical analyses: In the RAPID trial, 88% of patients with Excellent or Good cosmesis prior to RT had Excellent or Good scores at 3 years. Only patients with Excellent/Good cosmesis at baseline will be included in the current study. The proportion of women with Excellent/Good cosmesis at 1 and 2 years will be calculated. Using 80% power, a non-inferiority margin of 0.08 and a one-sided binomial test for non-inferiority and a significance level of 0.05, will require a sample size of 249 women with evaluable 2-yr cosmesis. 274 patients will be recruited to allow for a 10% drop-out rate. To ensure safety, a first interim analysis with Grade 2 or higher breast fibrosis as the primary endpoint, will be conducted when 50 patients have completed their 1-year assessment and repeated when 50 patients have completed their 2-year follow up. If the rate of Grade 2 or higher fibrosis exceeds 5% at either time point, trial accrual will be suspended.
Feasibility: Over 600 women eligible for this protocol receive RT in Alberta each year. If 30% accept study participation, accrual will be complete in <2 years.
- Conditions
- Breast Cancer
- Being tested
- APBI 27Gy in 5 fractions
- Keywords
- Radiation therapy, Accelerated partial breast irradiation (APBI), Breast conserving surgery, Stage 1
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APBI 27Gy in 5 fractionsRadiation
Patients will be treated with 3-D conformal, external beam, partial breast RT to deliver 27 Gy in 5 daily fractions using 3-5 beams on a linear accelerator. The target PTV will be the CT-visible seroma plus a 1cm margin to form the CTV (minus 5mm from skin and excluding chest wall) and a further 7mm to form the PTV. Real time review will ensure compliance with target and normal tissues dose constraints in this multi-institutional study. Any (or no) systemic therapy is permitted.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Single cohort to receive Accelerated Partial Breast Irradiation (APBI) 27Gy in 5 fractions Receives: Radiation: APBI 27Gy in 5 fractions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Excellent or Good Global cosmetic score
Global cosmetic score assessed by trained observers and patients themselves using the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer rating system for cosmetic assessment; rate of deterioration from Excellent/Good to Fair Poor. This will be augmented by assessment of clinical photographs prior to and at 1 and 2 years after radiation therapy (RT).
Measured: 2 years
Secondary outcomes (3)
Breast induration
Radiation Therapy Oncology Group (RTOG) Late Radiation Morbidity Scoring Scheme, rate of Grade 2+ subcutaneous fibrosis
Measured: 2 years
Breast pain
Patient reported average and worst pain in the treated breast over the week prior to assessment
Measured: 2 years
Local recurrence
Any new invasive or in situ breast cancer within the ipsilateral breast
Measured: 2 and 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2016 (estimated)
- Study startMay 2016
- Primary completionJul 2021 (estimated)
- Study completionJul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 2 - Irradiation
- Masking
- None (open label)
- Enrolment
- 274 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Petra Grendarova, MD, Principal investigator, Tom Baker Cancer Centre, Alberta Health Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02681107
- Sponsor's protocol ID
- HREBA.CC-16-0006
- Other IDs
- No. 11629-27/5-01
- Acronym
- ACCEL
- Status last verified
- Feb 2019
- First submitted
- 10 Feb 2016
- Last updated
- 21 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: At least one peer-review publication will be prepared by the investigators following the conclusion of the study. In addition, an abstract to report interim results following the 1-year, interim cosmetic evaluation may be submitted to the annual Canadian Association of Radiation Oncology and/or San Antonio Breast Cancer Symposium scientific meetings. Authorship will include the named investigators involved in the development of the grant proposal plus additional authors proportional to subject accrual, participation in the cosmetic photograph review panels and/or other contributions to study analysis or success.
Publications
Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013 Nov 10;31(32):4038-45. doi: 10.1200/JCO.2013.50.5511. Epub 2013 Jul 8.
PubMed 23835717
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated Partial Breast Irradiation Using Five Daily Fractions: A Single Arm, Phase II, Prospective Cohort Study to Examine Cosmetic Outcomes and Toxicity (The ACCEL Trial)
- ClinicalTrials.gov ID
- NCT02681107
- Acronym / sponsor ID
- ACCEL / HREBA.CC-16-0006
- Conditions
- Breast Cancer
- Keywords
- Radiation therapy, Accelerated partial breast irradiation (APBI), Breast conserving surgery, Stage 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 274 participants (estimated)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Collaborators
- Alberta Cancer Foundation
- Study start
- May 2016 (actual)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Jul 2021 (estimated)
- First posted
- 12 Feb 2016 (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.
This study will test the safety of partial breast RT using 27Gy in 5 daily fractions which is expected to be equally tolerated as standard whole breast irradiation (WBI) based on radiobiologic modeling of the fibrosis response of normal tissues but be more convenient and less costly than 3-6 weeks of standard WBI. 274 women will be treated. Rates of fibrosis and cosmesis at 2 years will be compared to data already collected using standard WBI in the Canadian RAPID trial.
Detailed description
Background: Previously, accelerated partial breast irradiation (APBI) using 3D conformal external beam techniques to deliver 38.5Gy in 10, twice daily, fractions caused worse fibrosis and cosmetic deterioration than standard whole breast irradiation (WBI) following breast conserving surgery (BCS) for women with early breast cancer. Over the decade since the original APBI technique was designed, long-term outcomes of various breast RT fractionation regimens have become available and suggest that normal tissue fibrosis and cosmesis varies with the radiobiological constant: α/β=2 rather than α/β=3.4 as previously estimated. Radiobiologic modeling using α/β=2, indicates that a dose of 27Gy in 5 daily treatments should result in comparable late effects as 42.5Gy in 16, or 50Gy in 25 fractions. This clinical trial will validate the safety of a short, convenient and less costly APBI using 27Gy in 5 daily fractions.
Objective: To determine the cosmetic and normal tissue outcomes of APBI using 3D-conformal RT with 27Gy in 5 fractions over 1 week.
Methods: A single-arm, phase II, non-inferiority, prospective study will be conducted. 274 women with newly diagnosed, invasive or in-situ ductal carcinoma treated with BCS and sentinel lymph node biopsy (or axillary dissection) who are candidates for WBI alone, will be treated. Subjects will be age 50 years and older, with tumors less than 3cm diameter, with negative margins and nodes and with excellent or good baseline cosmetic outcome following BCS. Patients with extensive ductal carcinoma in-situ, BRCA mutations, Grade 3 cancers with lymphatic or vascular invasion, or lobular carcinoma will be excluded. These selection criteria are similar to the Canadian RAPID trial. In the first phase of the study, 150 patients will be recruited and interim analyses will be conducted to rule out unacceptable toxicity at 2 years.
Study endpoints: The primary endpoint will be the proportion of women who retain an Excellent or Good cosmetic score at 2 years using the EORTC Cosmetic Rating System and clinical photographs taken prior to, and at 1 and 2 years after RT. Secondary endpoints will include rates and grades of breast fibrosis, induration, telangiectasia, breast pain, ipsilateral breast tumor recurrence, overall and breast cancer-specific survival and subsequent mastectomy rates.
Sample size, statistical analyses: In the RAPID trial, 88% of patients with Excellent or Good cosmesis prior to RT had Excellent or Good scores at 3 years. Only patients with Excellent/Good cosmesis at baseline will be included in the current study. The proportion of women with Excellent/Good cosmesis at 1 and 2 years will be calculated. Using 80% power, a non-inferiority margin of 0.08 and a one-sided binomial test for non-inferiority and a significance level of 0.05, will require a sample size of 249 women with evaluable 2-yr cosmesis. 274 patients will be recruited to allow for a 10% drop-out rate. To ensure safety, a first interim analysis with Grade 2 or higher breast fibrosis as the primary endpoint, will be conducted when 50 patients have completed their 1-year assessment and repeated when 50 patients have completed their 2-year follow up. If the rate of Grade 2 or higher fibrosis exceeds 5% at either time point, trial accrual will be suspended.
Feasibility: Over 600 women eligible for this protocol receive RT in Alberta each year. If 30% accept study participation, accrual will be complete in <2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 2 - Irradiation
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Radiation: APBI 27Gy in 5 fractionsSingle cohort to receive Accelerated Partial Breast Irradiation (APBI) 27Gy in 5 fractions |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female, with new invasive or in-situ ductal carcinoma of the breast
- Treated with Breast conserving surgery (BCS) with negative margins
- pN0 on sentinel node biopsy or axillary dissection; cN0 if DCIS alone
- Maximum pathologic tumor diameter is 3.0 cm (invasive or DCIS)
- No clinical or imaging evidence of distant metastases
Key exclusion criteria (13 listed)
- Age < 50 years at diagnosis
- BRCA 1 or 2 pathogenic mutation
- Pathologic tumor diameter >3cm (including DCIS+invasive disease)
- Lobular histology alone
- Triple negative (ER-, PR-, HER2-) or HER2 overexpressing disease
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 |
|---|---|---|
| APBI 27Gy in 5 fractionsPatients will be treated with 3-D conformal, external beam, partial breast RT to deliver 27 Gy in 5 daily fractions using 3-5 beams on a linear accelerator. The target PTV will be the CT-visible seroma plus a 1cm margin to form the CTV (minus 5mm from skin and excluding chest wall) and a further 7mm to form the PTV. Real time review will ensure compliance with target and normal tissues dose constraints in this multi-institutional study. Any (or no) systemic therapy is permitted. | Radiation | Single Arm |
Primary outcome
Rate of Excellent or Good Global cosmetic score
Time frame: 2 years
Global cosmetic score assessed by trained observers and patients themselves using the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer rating system for cosmetic assessment; rate of deterioration from Excellent/Good to Fair Poor. This will be augmented by assessment of clinical photographs prior to and at 1 and 2 years after radiation therapy (RT).
3 secondary outcomes
Breast induration
Time frame: 2 years
Breast pain
Time frame: 2 years
Local recurrence
Time frame: 2 and 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2019.
- Background: PubMed 23835717Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013 Nov 10;31(32):4038-45. doi: 10.1200/JCO.2013.50.5511. Epub 2013 Jul 8.
- Individual participant dataSharing planned: Yes. At least one peer-review publication will be prepared by the investigators following the conclusion of the study. In addition, an abstract to report interim results following the 1-year, interim cosmetic evaluation may be submitted to the annual Canadian Association of Radiation Oncology and/or San Antonio Breast Cancer Symposium scientific meetings. Authorship will include the named investigators involved in the development of the grant proposal plus additional authors proportional to subject accrual, participation in the cosmetic photograph review panels and/or other contributions to study analysis or success.
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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.
Mark Lesiuk, BSc contact
Petra Grendarova, MD principal investigator
Tom Baker Cancer Centre, Alberta Health Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing APBI 27Gy in 5 fractions in people with Breast Cancer, run by AHS Cancer Control Alberta at 1 site in Canada.
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 10 inclusion and 13 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 21 Feb 2019. 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 Canada. 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.
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 Petra Grendarova, MD (403-521-3105, petra.grendarova@ahs.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Excellent or Good Global cosmetic score (time frame: 2 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 NCT02681107, which also lists 1 linked publication.
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 21 Feb 2019.