Breast CancerPhase 3NCT05774678
Trial Of PreoperAtive Radiation (TOPAz): A Randomized Trial Comparing Hypofractionated Versus Conventionally Fractionated Preoperative Radiation Followed by Mastectomy With Immediate Autologous Breast Reconstruction With Integrated Tissue Nanomechanical Phenotype Evaluation
A Phase 3 study testing Group 1 (preoperative radiation hypofractionated) and Group 2 (preoperative radiation conventionally fractionated) in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To compare the outcomes of and responses to 2 different radiation therapy schedules (the standard radiation amount and number of doses versus less radiation and fewer doses) that are being given before having breast cancer surgery (cancer removal and reconstruction). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Group 1 (preoperative radiation hypofractionated) and Group 2 (preoperative radiation conventionally fractionated)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Apr 2023to 1 Nov 2028
- Phase
- Phase 3
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Histologic diagnosis of invasive breast cancer (cytologic or histologic confirmation of nodal metastasis is sufficient to establish this eligibility criteria).
- Clinical and/or pathologic stage T3-T4c OR N1-N3; for the IBC pilot cohort only, the stage requirement is T4d, any N, M1
- Mastectomy is the planned oncologic surgery but has not yet been performed at the time of protocol enrollment
- Autologous (i.e. tissue-based) reconstruction is planned with either a free or rotational flap.
- For patients with HER2 positive, non-IBC breast cancer treated with neoadjuvant chemotherapy, one of the following criteria must be met:
Show all 10Show fewer
- Residual invasive disease should be documented in either the breast or a regional nodal metastasis after neoadjuvant chemotherapy. This specific eligibility criteria can be satisfied by the post-chemotherapy standard of care breast biopsy. For this matter, the patient may be enrolled on the trial prior to biopsy. If the biopsy does not show residual invasive disease, then the patient will not proceed with protocol-directed therapy and will be removed and replaced from the study.
- Medical oncologist has documented a discussion in the chart about potential risks of proceeding with PreMRT with regard to impact on adjuvant systemic therapy decisions and the patient has opted to proceed with trial enrollment
- For T4d pilot cohort patients, post-chemotherapy, pre-radiation ultrasound must demonstrate at least partial response in the breast and regional lymph nodes and no suspicious infraclavicular, internal mammary, and supraclavicular lymph nodes.
- Ability to provide written informed consent in accordance with institutional policies.
Who cannot join
- Patients undergoing treatment for recurrent breast cancer in the index breast or lymph nodes.
- History of therapeutic irradiation to the breast, lower neck, mediastinum or other area(s) that will overlap with the affected breast.
- Presence of active scleroderma
- Patients who are pregnant.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Benjamin D. Smith, MD, 713-563-2380, bsmith3@mdanderson.org
Benjamin D. Smith, MD
About this study
To compare the outcomes of and responses to 2 different radiation therapy schedules (the standard radiation amount and number of doses versus less radiation and fewer doses) that are being given before having breast cancer surgery (cancer removal and reconstruction).
Read the detailed description
Primary Objectives:
--To compare BREAST-Q satisfaction with breasts 18 months after reconstructive surgery for patients randomized to HF-PreMRT versus CF-PreMRT. We hypothesize that HF-PreMRT will be superior to CF-PreMRT with regard to this endpoint.
Secondary Objectives:
- To compare oncologic outcomes following HF-PreMRT versus CF-PreMRT, including residual cancer burden, local-regional control, disease-free survival, and overall survival.
- To compare surgical outcomes following HF-PreMRT versus CF-PreMRT, including surgical complications, flap loss, difficulty of reconstructive surgery, number of reoperations, and aesthetic outcomes including photographic assessment of the reconstructed breast.
- To compare radiation outcomes following HF-PreMRT versus CF-PreMRT, including acute and late toxicities and fibrosis.
- To compare health services research outcomes following HF-PreMRT versus CF-PreMRT, including financial toxicity, work productivity and disability, total cost of care, complicationrelated cost of care, and health utility.
- To compare patient-reported quality of life and toxicities following HF-PreMRT versus CFPreMRT.
- To compare patient-reported quality of life and toxicities following HF-PreMRT versus CFPreMRT.
- To evaluate associations between the radiation treatment plan parameters and surgical, radiation, health services, and patient-reported outcomes.
- To evaluate nanomechanical properties of the breast cancer before and after radiation and their association with oncologic outcomes
- To evaluate nanomechanical properties of the breast normal tissue after radiation and their association with surgical and radiation outcomes.
- To evaluate the association of germline polymorphisms, including the pro-fibrotic cytokine transforming growth factor-beta (TGF-β), with circulating serum TGF- levels during and after radiation and toxicities of radiation and reconstruction, particularly fibrotic complications.
- To characterize pre- and post-radiation tumor and nodal tissue by single cell sequencing, whole genome, whole exome, and targeted sequencing, and digital spatial profiling for immune landscape, radiation resistance signatures, microenvironmental and tumor genome profiles and correlate radiation induced changes to tumor and patient characteristics and residual cancer burden.
- To characterize pre- and post-radiation tumor and nodal tissue by single cell sequencing, whole genome, whole exome, and targeted sequencing, and digital spatial profiling for immune landscape, radiation resistance signatures, microenvironmental and tumor genome profiles and correlate radiation induced changes to tumor and patient characteristics and residual cancer burden.
- To characterize irradiated normal breast and nodal tissues for genomic, proteomic, and metabolomic profiles and correlate these to tumor and patient characteristics, tumor burden, and toxicity
- To characterize irradiated normal breast and nodal tissues for genomic, proteomic, and metabolomic profiles and correlate these to tumor and patient characteristics, tumor burden, and toxicity.
- To compare surgical, radiation, and health services outcomes for patients treated with PreMRT on this trial to a matched cohort of patients treated with standard post-mastectomy radiation with breast reconstruction on the SAPHIRE protocol (2016-0142).
- To compare translational data for patients treated with PreMRT on this trial to a matched cohort of patients treated with standard post-mastectomy radiation with breast reconstruction on the SAPHIRE protocol (2016-0142).
- Conditions
- Breast Cancer
- Being tested
- Group 1 (preoperative radiation hypofractionated), Group 2 (preoperative radiation conventionally fractionated)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group 1 (preoperative radiation hypofractionated)Radiation
radiation schedules/regimens before your scheduled breast surgery
Group 2 (preoperative radiation conventionally fractionated)Other
radiation schedules/regimens before your scheduled breast surgery
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (preoperative radiation hypofractionated) | Experimental | Participants will receive the standard number of radiation treatment doses Receives: Radiation: Group 1 (preoperative radiation hypofractionated); Other: Group 2 (preoperative radiation conventionally fractionated) |
| Group 2 (preoperative radiation conventionally fractionated) | Experimental | Participants will receive the standard number of radiation treatment doses Receives: Radiation: Group 1 (preoperative radiation hypofractionated); Other: Group 2 (preoperative radiation conventionally fractionated) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start5 Apr 2023
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Artidis
- Responsible party
- Sponsor
- Investigators
- Benjamin D. Smith, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05774678
- Sponsor's protocol ID
- 2022-0880
- Other IDs
- NCI-2023-01985
- Status last verified
- Oct 2026
- First submitted
- 28 Feb 2023
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Schaverien MV, Singh P, Kuerer HM, Akay CL, Chavez-MacGregor M, Chu CK, Clemens MW, Qiao W, Smith BD, Hoffman KE. Comparison of Outcomes of Microsurgical Breast Reconstruction after Premastectomy and Postmastectomy Radiation Therapy. J Am Coll Surg. 2025 Oct 1;241(4):535-549. doi: 10.1097/XCS.0000000000001444. Epub 2025 Sep 16.
PubMed 40366003Schaverien MV, Singh P, Smith BD, Qiao W, Akay CL, Bloom ES, Chavez-MacGregor M, Chu CK, Clemens MW, Colen JS, Ehlers RA, Hwang RF, Joyner MM, Largo RD, Mericli AF, Mitchell MP, Shuck JW, Tamirisa N, Tripathy D, Villa MT, Woodward WA, Zacharia R, Kuerer HM, Hoffman KE. Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e245217. doi: 10.1001/jamanetworkopen.2024.5217.
PubMed 38578640
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial Of PreoperAtive Radiation (TOPAz): A Randomized Trial Comparing Hypofractionated Versus Conventionally Fractionated Preoperative Radiation Followed by Mastectomy With Immediate Autologous Breast Reconstruction With Integrated Tissue Nanomechanical Phenotype Evaluation
- ClinicalTrials.gov ID
- NCT05774678
- Acronym / sponsor ID
- 2022-0880
- Conditions
- Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Artidis
- Study start
- 5 Apr 2023 (actual)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Nov 2028 (estimated)
- First posted
- 20 Mar 2023 (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.
To compare the outcomes of and responses to 2 different radiation therapy schedules (the standard radiation amount and number of doses versus less radiation and fewer doses) that are being given before having breast cancer surgery (cancer removal and reconstruction).
Detailed description
Primary Objectives:
--To compare BREAST-Q satisfaction with breasts 18 months after reconstructive surgery for patients randomized to HF-PreMRT versus CF-PreMRT. We hypothesize that HF-PreMRT will be superior to CF-PreMRT with regard to this endpoint.
Secondary Objectives:
- To compare oncologic outcomes following HF-PreMRT versus CF-PreMRT, including residual cancer burden, local-regional control, disease-free survival, and overall survival.
- To compare surgical outcomes following HF-PreMRT versus CF-PreMRT, including surgical complications, flap loss, difficulty of reconstructive surgery, number of reoperations, and aesthetic outcomes including photographic assessment of the reconstructed breast.
- To compare radiation outcomes following HF-PreMRT versus CF-PreMRT, including acute and late toxicities and fibrosis.
- To compare health services research outcomes following HF-PreMRT versus CF-PreMRT, including financial toxicity, work productivity and disability, total cost of care, complicationrelated cost of care, and health utility.
- To compare patient-reported quality of life and toxicities following HF-PreMRT versus CFPreMRT.
- To compare patient-reported quality of life and toxicities following HF-PreMRT versus CFPreMRT.
- To evaluate associations between the radiation treatment plan parameters and surgical, radiation, health services, and patient-reported outcomes.
- To evaluate nanomechanical properties of the breast cancer before and after radiation and their association with oncologic outcomes
- To evaluate nanomechanical properties of the breast normal tissue after radiation and their association with surgical and radiation outcomes.
- To evaluate the association of germline polymorphisms, including the pro-fibrotic cytokine transforming growth factor-beta (TGF-β), with circulating serum TGF- levels during and after radiation and toxicities of radiation and reconstruction, particularly fibrotic complications.
- To characterize pre- and post-radiation tumor and nodal tissue by single cell sequencing, whole genome, whole exome, and targeted sequencing, and digital spatial profiling for immune landscape, radiation resistance signatures, microenvironmental and tumor genome profiles and correlate radiation induced changes to tumor and patient characteristics and residual cancer burden.
- To characterize pre- and post-radiation tumor and nodal tissue by single cell sequencing, whole genome, whole exome, and targeted sequencing, and digital spatial profiling for immune landscape, radiation resistance signatures, microenvironmental and tumor genome profiles and correlate radiation induced changes to tumor and patient characteristics and residual cancer burden.
- To characterize irradiated normal breast and nodal tissues for genomic, proteomic, and metabolomic profiles and correlate these to tumor and patient characteristics, tumor burden, and toxicity
- To characterize irradiated normal breast and nodal tissues for genomic, proteomic, and metabolomic profiles and correlate these to tumor and patient characteristics, tumor burden, and toxicity.
- To compare surgical, radiation, and health services outcomes for patients treated with PreMRT on this trial to a matched cohort of patients treated with standard post-mastectomy radiation with breast reconstruction on the SAPHIRE protocol (2016-0142).
- To compare translational data for patients treated with PreMRT on this trial to a matched cohort of patients treated with standard post-mastectomy radiation with breast reconstruction on the SAPHIRE protocol (2016-0142).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 (preoperative radiation hypofractionated) | Experimental | Radiation: Group 1 (preoperative radiation hypofractionated), Other: Group 2 (preoperative radiation conventionally fractionated)Participants will receive the standard number of radiation treatment doses |
| Group 2 (preoperative radiation conventionally fractionated) | Experimental | Radiation: Group 1 (preoperative radiation hypofractionated), Other: Group 2 (preoperative radiation conventionally fractionated)Participants will receive the standard number of radiation treatment doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18 years or older
- Histologic diagnosis of invasive breast cancer (cytologic or histologic confirmation of nodal metastasis is sufficient to establish this eligibility criteria).
- Clinical and/or pathologic stage T3-T4c OR N1-N3; for the IBC pilot cohort only, the stage requirement is T4d, any N, M1
- Mastectomy is the planned oncologic surgery but has not yet been performed at the time of protocol enrollment
- Autologous (i.e. tissue-based) reconstruction is planned with either a free or rotational flap.
Key exclusion criteria (4 listed)
- Patients undergoing treatment for recurrent breast cancer in the index breast or lymph nodes.
- History of therapeutic irradiation to the breast, lower neck, mediastinum or other area(s) that will overlap with the affected breast.
- Presence of active scleroderma
- Patients who are pregnant.
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 |
|---|---|---|
| Group 1 (preoperative radiation hypofractionated)radiation schedules/regimens before your scheduled breast surgery | Radiation | Group 1 (preoperative radiation hypofractionated), Group 2 (preoperative radiation conventionally fractionated) |
| Group 2 (preoperative radiation conventionally fractionated)radiation schedules/regimens before your scheduled breast surgery | Other | Group 1 (preoperative radiation hypofractionated), Group 2 (preoperative radiation conventionally fractionated) |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion; an average of 1 year.
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 6 Oct 2026.
- Derived from this study: PubMed 40366003Schaverien MV, Singh P, Kuerer HM, Akay CL, Chavez-MacGregor M, Chu CK, Clemens MW, Qiao W, Smith BD, Hoffman KE. Comparison of Outcomes of Microsurgical Breast Reconstruction after Premastectomy and Postmastectomy Radiation Therapy. J Am Coll Surg. 2025 Oct 1;241(4):535-549. doi: 10.1097/XCS.0000000000001444. Epub 2025 Sep 16.
- Derived from this study: PubMed 38578640Schaverien MV, Singh P, Smith BD, Qiao W, Akay CL, Bloom ES, Chavez-MacGregor M, Chu CK, Clemens MW, Colen JS, Ehlers RA, Hwang RF, Joyner MM, Largo RD, Mericli AF, Mitchell MP, Shuck JW, Tamirisa N, Tripathy D, Villa MT, Woodward WA, Zacharia R, Kuerer HM, Hoffman KE. Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e245217. doi: 10.1001/jamanetworkopen.2024.5217.
- M D Anderson Cancer CenterLink provided by the sponsor.
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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.
Benjamin D. Smith, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Group 1 (preoperative radiation hypofractionated) and Group 2 (preoperative radiation conventionally fractionated) in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
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 4 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: looking for participants now, as of the sponsor's last update on 6 Oct 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 United States. 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 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?
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?
Contact Benjamin D. Smith, MD ((713) 563-2380, bsmith3@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 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 NCT05774678, which also lists 2 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 6 Oct 2026.