High-Risk CancerTRIONCT03978663
Three Fraction Radiation to Induce Immuno-Oncologic Response
A study testing Neoadjuvant radiotherapy in people with High-Risk Cancer and Locally Advanced Breast Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
Patients with high risk breast cancers (any locally advanced breast cancer patient defined as Stages IIB-III [excluding inflammatory breast cancer] with stage IIA being eligible for triple negative and HER2-positive breast cancers) will receive neoadjuvant radiation to any portion of their tumour in three fractions in… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- High-Risk Cancer, Locally Advanced Breast Cancer
- What is being tested?
- Neoadjuvant radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 2 Sep 2020to Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any biopsy-proven locally advanced breast cancer patient defined as Stages IIB-III (excluding inflammatory breast cancer). Stage IIA is eligible for triple negative and HER2-positive breast cancers
- Invasive mammary carcinoma of any subtype excluding lobular, sarcomatous, or metaplastic subtypes, or with lobular features
- Plan to be treated with neoadjuvant chemotherapy
- Able to fit in/have MRI
- 18 years of age or older
- Able to tolerate core needle biopsies
- Able to provide informed consent
- No evidence of metastatic disease
Who cannot join
- Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery
- Prior treatment for current breast cancer
- Previous radiation therapy to the same breast
- Inflammatory breast carcinoma
- Invasive lobular carcinoma or invasive mammary carcinoma with lobular, sarcomatous, or metaplastic subtypes, or with lobular features
- Recurrent breast cancer
Show all 16Show fewer
- Bilateral breast cancer
- Evidence of distant metastatic disease
- Collagen vascular disease (particularly lupus, scleroderma, dermatomyositis, psoriatic arthritis)
- Any other malignancy at any site (except non-melanomatous skin cancer) <5 years prior to study enrollment
- Inability to lay prone with arms above the head for extended periods of time
- Inability to fit in/have an MRI
- Inability to tolerate core needle biopsies
- Pregnant or lactating
- Under 18 years of age
- Inability or unwillingness to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Use of Stereotactic Radiation Therapy Prior to Neoadjuvant Chemotherapy for High-risk Breast Carcinoma (a SIGNAL Series Clinical Trial): Three Fraction Radiation to Induce Immuno-Oncologic Response (TRIO Trial)
Patients with high risk breast cancers (any locally advanced breast cancer patient defined as Stages IIB-III [excluding inflammatory breast cancer] with stage IIA being eligible for triple negative and HER2-positive breast cancers) will receive neoadjuvant radiation to any portion of their tumour in three fractions in order to act as an immune primer. Radiation will be delivered to a portion of the tumour in three fractions. The patient will be positioned prone as per the SIGNAL 2.0 protocol. The patient will then go on to standard of care treatment (neoadjuvant chemotherapy and surgery) followed by whole-breast radiation as needed. Pathologic complete response will be the primary outcome. Immune markers will also be evaluated.
Read the detailed description
Patients eligible for neoadjuvant chemotherapy for locally advanced stage III (non-inflammatory) breast cancer or stage IIb (triple negative or Her2+) breast cancers will be approached to participate in this single arm trial. Patients with staging investigations ruling out distant disease will be approached to participate and will undergo pre-treatment image guided core biopsy and blood samples for molecular correlative studies, followed by hypofractionated radiation (delivered prone) to entire tumor with dose constraints to skin, critical organs and contralateral breast, plus a 0.5 cm PTV. As much of the tumor that can receive planned dose of 8 Gy per fraction x 3 fractions every second day, with fall off dose to 4 Gy per fraction x 3 fractions for PTV margin. Two weeks following completion of radiation, patients will undergo a second image guided core needle biopsy of tumor and blood sample. They will then begin standard neoadjuvant chemotherapy (anthracycline and taxane based), followed by a third tissue biopsy under image guidance of any residual tumor and blood sample and then standard surgery (breast conserving or lumpectomy). This will be followed by standard whole breast radiation (50 Gy in 25 fractions). Herceptin therapy and hormonal therapy will be administered as per clinical standard when indicated. Primary outcome will be measured as pathological complete response to treatment, and secondary outcomes will include toxicity, immune markers (tumor infiltrating lymphocytes, PD-1 and PD-L1 up-regulation and changes to the circulating lymphocyte counts.
- Conditions
- High-Risk Cancer, Locally Advanced Breast Cancer
- Being tested
- Neoadjuvant radiotherapy
- Keywords
- locally advanced breast cancer, immune priming, radiation therapy, neoadjuvant radiation, radiotherapy, immuno-oncology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant radiotherapyRadiation
Neoadjuvant radiation therapy delivered to a portion of the index tumour for high-risk breast carcinoma for immune priming prior to neoadjuvant radiation
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant radiotherapy | Experimental | 3 doses of stereotactic radiotherapy administered prior to neoadjuvant chemotherapy in high-risk breast cancers. Receives: Radiation: Neoadjuvant radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic complete response
Pathologic complete response rates after neoadjuvant radiotherapy and chemotherapy will be evaluated.
Measured: Measured at time of surgery, typically 6 months after enrollment in trial.
Secondary outcomes (9)
Response rates in the primary post chemotherapy by imaging
Response rates in the primary post chemotherapy by MRI +/- PET scan compared to pre-neoadjuvant radiation imaging
Measured: Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery, typically 6 months after enrollment in trial.
Response rates in the axillary nodes post chemotherapy by imaging and pathology
Absence of any invasive breast cancer cells in any tissue at time of surgery
Measured: Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery (imaging) and at time of surgery, typically 6 months after enrollment in trial.
Immune priming
Immune priming as measured by amount of tumour infiltrating lymphocytes (CD8) into tumour specimen, as well as the expression of immune markers (PDL1, Fox3) and immune panel in blood (CD4, CD8, neutrophil, and macrophage counts). Angiogenesis will be examined using the CD31 or VEGF-a cell markers, proliferation will be examined using the Ki67 marker, hypoxia will be examined using the Carbonic Anhydrase 9 (CAH IX), or HIF1/HIF2 markers, apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.
Measured: Measured 14-20 days after the last dose of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy.
Radiation toxicity
Toxicity to surrounding breast and skin tissue, defined by ≥ grade 2 fibrosis.
Measured: Measured at study enrollment, at first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.
Surgical wound healing and the overall complication rate.
Percentage of patients experiencing wound infection that requires wound to be opened and/or packed.
Measured: Measured at the first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.
Local recurrence rates
Ipsilateral breast recurrence rate.
Measured: Disease status will be evaluated at routine patient follow-up appointments, including yearly mammography. Will be reported at year 3.
Ability of imaging to predict patient response to radiotherapy.
Correlation between complete clinical response on imaging and pathological complete response.
Measured: Pre-treatment imaging to be done after study enrollment (baseline) and 14-20 days after the last dose of neoadjuvant radiation has been delivered.
Ability of imaging markers to predict response to radiotherapy
Ability of FDG uptake, choline levels, perfusion, and ADC obtained from post-radiotherapy imaging to predict tissue response to high dose radiotherapy.
Measured: Pre-treatment imaging to be done after study enrollment (baseline measurements) and 14-20 days after the last dose of neoadjuvant radiation has been delivered.
Ability to predict pathological response to treatment based on tumour genetics
Ability to predict pathological response to treatment based on microarray analysis of tumor gene expression.
Measured: Tissue samples for analysis will be taken 14-20 days after completion of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy and will be compared with tissue taken prior to the start of neoadjuvant radiation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2019
- Study start2 Sep 2020
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-Risk 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
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Muriel Brackstone, MD PhD, Principal investigator, London Health Sciences Centre/Lawson Health Research InstituteMichael Lock, MD, Study chair, London Health Sciences Centre/London Regional Cancer ProgramBrian Yaremko, MD, Study chair, London Health Sciences Centre/London Regional Cancer Program
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03978663
- Sponsor's protocol ID
- 112626
- Acronym
- TRIO
- Status last verified
- Feb 2026
- First submitted
- 1 Jun 2019
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Use of Stereotactic Radiation Therapy Prior to Neoadjuvant Chemotherapy for High-risk Breast Carcinoma (a SIGNAL Series Clinical Trial): Three Fraction Radiation to Induce Immuno-Oncologic Response (TRIO Trial)
- ClinicalTrials.gov ID
- NCT03978663
- Acronym / sponsor ID
- TRIO / 112626
- Conditions
- High-Risk Cancer, Locally Advanced Breast Cancer
- Keywords
- locally advanced breast cancer, immune priming, radiation therapy, neoadjuvant radiation, radiotherapy, immuno-oncology
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 7 Jun 2019 (actual)
- 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.
Patients with high risk breast cancers (any locally advanced breast cancer patient defined as Stages IIB-III [excluding inflammatory breast cancer] with stage IIA being eligible for triple negative and HER2-positive breast cancers) will receive neoadjuvant radiation to any portion of their tumour in three fractions in order to act as an immune primer. Radiation will be delivered to a portion of the tumour in three fractions. The patient will be positioned prone as per the SIGNAL 2.0 protocol. The patient will then go on to standard of care treatment (neoadjuvant chemotherapy and surgery) followed by whole-breast radiation as needed. Pathologic complete response will be the primary outcome. Immune markers will also be evaluated.
Detailed description
Patients eligible for neoadjuvant chemotherapy for locally advanced stage III (non-inflammatory) breast cancer or stage IIb (triple negative or Her2+) breast cancers will be approached to participate in this single arm trial. Patients with staging investigations ruling out distant disease will be approached to participate and will undergo pre-treatment image guided core biopsy and blood samples for molecular correlative studies, followed by hypofractionated radiation (delivered prone) to entire tumor with dose constraints to skin, critical organs and contralateral breast, plus a 0.5 cm PTV. As much of the tumor that can receive planned dose of 8 Gy per fraction x 3 fractions every second day, with fall off dose to 4 Gy per fraction x 3 fractions for PTV margin. Two weeks following completion of radiation, patients will undergo a second image guided core needle biopsy of tumor and blood sample. They will then begin standard neoadjuvant chemotherapy (anthracycline and taxane based), followed by a third tissue biopsy under image guidance of any residual tumor and blood sample and then standard surgery (breast conserving or lumpectomy). This will be followed by standard whole breast radiation (50 Gy in 25 fractions). Herceptin therapy and hormonal therapy will be administered as per clinical standard when indicated. Primary outcome will be measured as pathological complete response to treatment, and secondary outcomes will include toxicity, immune markers (tumor infiltrating lymphocytes, PD-1 and PD-L1 up-regulation and changes to the circulating lymphocyte counts.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant radiotherapy | Experimental | Radiation: Neoadjuvant radiotherapy3 doses of stereotactic radiotherapy administered prior to neoadjuvant chemotherapy in high-risk breast cancers. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Any biopsy-proven locally advanced breast cancer patient defined as Stages IIB-III (excluding inflammatory breast cancer). Stage IIA is eligible for triple negative and HER2-positive breast cancers
- Invasive mammary carcinoma of any subtype excluding lobular, sarcomatous, or metaplastic subtypes, or with lobular features
- Plan to be treated with neoadjuvant chemotherapy
- Able to fit in/have MRI
- 18 years of age or older
Key exclusion criteria (16 listed)
- Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery
- Prior treatment for current breast cancer
- Previous radiation therapy to the same breast
- Inflammatory breast carcinoma
- Invasive lobular carcinoma or invasive mammary carcinoma with lobular, sarcomatous, or metaplastic subtypes, or with lobular features
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 |
|---|---|---|
| Neoadjuvant radiotherapyNeoadjuvant radiation therapy delivered to a portion of the index tumour for high-risk breast carcinoma for immune priming prior to neoadjuvant radiation | Radiation | Neoadjuvant radiotherapy |
Primary outcome
Pathologic complete response
Time frame: Measured at time of surgery, typically 6 months after enrollment in trial.
Pathologic complete response rates after neoadjuvant radiotherapy and chemotherapy will be evaluated.
9 secondary outcomes
Response rates in the primary post chemotherapy by imaging
Time frame: Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery, typically 6 months after enrollment in trial.
Response rates in the axillary nodes post chemotherapy by imaging and pathology
Time frame: Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery (imaging) and at time of surgery, typically 6 months after enrollment in trial.
Immune priming
Time frame: Measured 14-20 days after the last dose of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy.
Radiation toxicity
Time frame: Measured at study enrollment, at first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.
Surgical wound healing and the overall complication rate.
Time frame: Measured at the first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.
Local recurrence rates
Time frame: Disease status will be evaluated at routine patient follow-up appointments, including yearly mammography. Will be reported at year 3.
Ability of imaging to predict patient response to radiotherapy.
Time frame: Pre-treatment imaging to be done after study enrollment (baseline) and 14-20 days after the last dose of neoadjuvant radiation has been delivered.
Ability of imaging markers to predict response to radiotherapy
Time frame: Pre-treatment imaging to be done after study enrollment (baseline measurements) and 14-20 days after the last dose of neoadjuvant radiation has been delivered.
Ability to predict pathological response to treatment based on tumour genetics
Time frame: Tissue samples for analysis will be taken 14-20 days after completion of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy and will be compared with tissue taken prior to the start of neoadjuvant radiation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
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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.
Muriel Brackstone, MD PhD principal investigator
London Health Sciences Centre/Lawson Health Research Institute
Michael Lock, MD study chair
London Health Sciences Centre/London Regional Cancer Program
Brian Yaremko, MD study chair
London Health Sciences Centre/London Regional Cancer Program
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neoadjuvant radiotherapy in people with High-Risk Cancer and Locally Advanced Breast Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's 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 8 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 20 Feb 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Pathologic complete response (time frame: Measured at time of surgery, typically 6 months after enrollment in trial.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Feb 2026.