Breast CancerPhase 1NCT04040569
A Phase I Dose Escalation Study of Single Fraction Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer
A Phase 1 study testing Radiomics on MRI in people with Breast Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Radiomics on MRI
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Dec 2019to Jul 2027
- Phase
- Phase 1
- 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
- Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer diagnosis
- Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam
- Age >/= 18 years old and female
- Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy
- Tumor must be unifocal
- The tumor must be visible on CT scan and/or preferably marked with clip(s) in tumor
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- Patients must undergo an MRI for work up to aid in tumor delineation and to rule out additional foci of disease. If additional foci of disease are present, they need to have a negative biopsy to proceed with treatment.If patient cannot have MRI, contrast enhanced digital mammography (CEDM) is allowed in place of MRI.
- Clinically and radiographically node negative on ultrasound of the axilla or MRI
- Estrogen receptor positive or Progesterone receptor positive and Her2neu negative
- Ability to understand and the willingness to sign a written informed consent.
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to the start of study and for the duration of radiation therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months
Who cannot join
- Multi-centric disease
- Prior RT to the involved breast
- Tumor size >3cm
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
- Patients who are pregnant or lactating due to the potential exposure to the fetus to radiation therapy and unknown effects of radiation therapy to lactating females
- Patients unable to have an MRI or contrast enhanced digital mammography (CEDM)
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- Prior ipsilateral breast cancer
- Tumor less than 5mm from the skin surface on clinical exam and/or radiographic imaging
- Patients with active Lupus or scleroderma
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390
About this study
The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction.
Read the detailed description
Preoperative stereotactic breast radiation may be beneficial as it offers the ability to target smaller treatment volumes than what has been achievable with adjuvant PBI (Nichols IJROBP 2010), track radiobiological response to radiation at time of surgical pathology, and allow the removal of all irradiated tissue to potentially minimize late effects.The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction. This would be accomplished on the CyberKnife or GammaPod. The GammaPod is a novel device dedicated to S-PBI utilizing a Cobalt-60 source (Yu Med Phys 2013), which offers a highly reproducible prone setup with a mean of 1.8mm of mismatch reported in 15 patients at the University of Maryland on consecutive scans (Yu JCO 2011). Implications of this research are far reaching, including determination of the maximally tolerated dose for preoperative S-PBI, pathologic complete response rates of early stage breast cancer to a predicted radioablative dose, radiographic markers of treatment response (radiomics), and translational research assessing mechanisms of immune and radiation response.
- Conditions
- Breast Cancer
- Being tested
- Radiomics on MRI
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiomics on MRIRadiation
Through extracting and analyzing a large number of features from medical imaging, radiomics has shown promising results in treatment outcome prediction for many diseases including breast cancer (45-50). UTSW physics group has developed several new radiomic approaches and radiomic features, such as a multi-objective radiomics model(51) and a new radiomic "Shell" feature(52). As an exploratory end point for this trial, the investigators will explore the application radiomics using pre-treatment MRI, treatment parameters and clinical characteristics as input to predict pathological response of radiation therapy (XRT) based on pathology report of surgical tissues and local recurrence.
| Study group | Role | What they receive |
|---|---|---|
| Single-fraction stereotactic partial breast radiotherapy | Experimental | The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac,Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. Receives: Radiation: Radiomics on MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reach the maximum tolerated dose (MTD)
The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac, Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. Done by escalating the dose of SBRT toward the tumorcidal dose of 38 Gy in fraction. Doses will be escalated an additional 3.5-4 Gy per treatment. The phase I portion of the study will be completed when either of the following events occur: 1) the MTD for a cohort is reached or 2) when delivery of a pre-determined highest dose of radiation (38 Gy) that has been deemed likely to be efficacious for treatment of early stage breast cancer is attained.Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Measured: 5 years
Secondary outcomes (7)
Cosmesis outcome
Photographs of both breasts will be taken and cosmesis form will be graded by the patient and the radiation oncologist at twelve months from the start of therapy and at yearly intervals thereafter and an independent panel established at UTSW Medical Center will evaluate cosmesis at the end of study.
Excellent: When compared to the untreated breast, there is minimal or no difference in the sizes, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance Good: There is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only mild change in the shape Fair: There is obvious difference in the size and shape of the treated breast. This change involves ¼ or less of the breast Poor: Marked change in the appearance of the treated breast involving more than ¼ of breast tissue
Measured: 5 years
Local Control
computed using Kaplan-Meier curves along with the 95% confidence interval
Measured: 5 years
Acute Toxicity
Exact binomial method will be used to calculate toxicity. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Measured: 90 Days
Late Toxicity
Exact binomial method will be used to calculate toxicity. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Measured: 24 Months
Rates of Surgical Morbidity
Number of patients with surgical morbidity
Measured: 5 years
Pathologic Complete Response Rates
Exact binomial method will be used to calculate the response rate.
Measured: 5 years
Distant Disease-Free Survival
computed using Kaplan-Meier curves along with the 95% confidence interval
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 posted31 Jul 2019
- Study start25 Dec 2019
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (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.
- More trials run by University of Texas Southwestern Medical 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All patients in each dose cohort will be treated as a single group for dose escalation. The starting dose for the dose escalation portion will be 30 Gy. Subsequent cohorts of patients will receive an additional 4 Gy per treatment. If significant toxicity is encountered at the starting dose, a de-escalation will occur (step -1) to 26.5 Gy. As we are currently concluding an adjuvant single fraction phase I protocol (ClinicalTrials.gov Identifier: NCT02685332) to 30 Gy in a single fraction for early stage breast cancer, if we meet our endpoints of this study, we will start our dose escalation at 34Gy instead of the 30 Gy, as safety of the 30 Gy arm will have already been established.
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asal Rahimi, University of Texas Southwestern Medical Center
- Investigators
- Asal Rahimi, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04040569
- Sponsor's protocol ID
- STU-2019-1183
- Status last verified
- Sep 2026
- First submitted
- 25 Jul 2019
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Rahimi A, Leitch M, Dogan B, Liu Y, Alluri P, Arbab M, Li X, Parsons DDM, Kim DWN, Wandrey N, Farr D, Seiler S, Unni N, Nguyen A, Wooldridge R, Chiu TD, Lu W, Stojadinovic S, Visak J, Nwachukwu C, Patel I, Morgan H, Bahrami S, Stein M, McArthur HL, Sahoo S, Timmerman R. Ablative Preoperative Single-Fraction Radiation Dose Escalation Among Patients With Breast Cancer: A Phase 1 Nonrandomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2543689. doi: 10.1001/jamanetworkopen.2025.43689.
PubMed 41236737
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Single Fraction Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT04040569
- Acronym / sponsor ID
- STU-2019-1183
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 25 Dec 2019 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 31 Jul 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.
The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction.
Detailed description
Preoperative stereotactic breast radiation may be beneficial as it offers the ability to target smaller treatment volumes than what has been achievable with adjuvant PBI (Nichols IJROBP 2010), track radiobiological response to radiation at time of surgical pathology, and allow the removal of all irradiated tissue to potentially minimize late effects.The purpose of this phase I trial is to evaluate dose-limiting toxicity while dose escalating single-fraction preoperative S-PBI to a presumed radioablative dose over 3 cohorts, starting with 30Gy in 1 fraction and advancing to 34Gy and 38Gy in 1 fraction. This would be accomplished on the CyberKnife or GammaPod. The GammaPod is a novel device dedicated to S-PBI utilizing a Cobalt-60 source (Yu Med Phys 2013), which offers a highly reproducible prone setup with a mean of 1.8mm of mismatch reported in 15 patients at the University of Maryland on consecutive scans (Yu JCO 2011). Implications of this research are far reaching, including determination of the maximally tolerated dose for preoperative S-PBI, pathologic complete response rates of early stage breast cancer to a predicted radioablative dose, radiographic markers of treatment response (radiomics), and translational research assessing mechanisms of immune and radiation response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All patients in each dose cohort will be treated as a single group for dose escalation. The starting dose for the dose escalation portion will be 30 Gy. Subsequent cohorts of patients will receive an additional 4 Gy per treatment. If significant toxicity is encountered at the starting dose, a de-escalation will occur (step -1) to 26.5 Gy. As we are currently concluding an adjuvant single fraction phase I protocol (ClinicalTrials.gov Identifier: NCT02685332) to 30 Gy in a single fraction for early stage breast cancer, if we meet our endpoints of this study, we will start our dose escalation at 34Gy instead of the 30 Gy, as safety of the 30 Gy arm will have already been established.
| Arm | Type | Receives |
|---|---|---|
| Single-fraction stereotactic partial breast radiotherapy | Experimental | Radiation: Radiomics on MRIThe primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac,Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Invasive epithelial (ductal, medullary, lobular, papillary, mucinous (colloid), or tubular) histologies of the breast 3 cm or less(T1-T2cN0) in women who have not undergone surgery or neoadjuvant endocrine or chemotherapy for current breast cancer diagnosis
- Tumor must not involve the overlying skin based on imaging evaluation and/or clinical exam
- Age >/= 18 years old and female
- Greatest Tumor dimension is 3cm or less based on US. MRI measurements can be included only if performed BEFORE the biopsy
- Tumor must be unifocal
Key exclusion criteria (9 listed)
- Multi-centric disease
- Prior RT to the involved breast
- Tumor size >3cm
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
- Patients who are pregnant or lactating due to the potential exposure to the fetus to radiation therapy and unknown effects of radiation therapy to lactating females
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 |
|---|---|---|
| Radiomics on MRIThrough extracting and analyzing a large number of features from medical imaging, radiomics has shown promising results in treatment outcome prediction for many diseases including breast cancer (45-50). UTSW physics group has developed several new radiomic approaches and radiomic features, such as a multi-objective radiomics model(51) and a new radiomic "Shell" feature(52). As an exploratory end point for this trial, the investigators will explore the application radiomics using pre-treatment MRI, treatment parameters and clinical characteristics as input to predict pathological response of radiation therapy (XRT) based on pathology report of surgical tissues and local recurrence. | Radiation | Single-fraction stereotactic partial breast radiotherapy |
Primary outcome
Reach the maximum tolerated dose (MTD)
Time frame: 5 years
The primary objective is to escalate the dose of 1 fraction stereotactic partial breast radiotherapy utilizing the MR Linac, Gammapod or Cyberknife system to an ablative dose in the pre-operative setting to the primary tumor without exceeding the maximum tolerated dose in patients with early stage breast cancer. Done by escalating the dose of SBRT toward the tumorcidal dose of 38 Gy in fraction. Doses will be escalated an additional 3.5-4 Gy per treatment. The phase I portion of the study will be completed when either of the following events occur: 1) the MTD for a cohort is reached or 2) when delivery of a pre-determined highest dose of radiation (38 Gy) that has been deemed likely to be efficacious for treatment of early stage breast cancer is attained.Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
7 secondary outcomes
Cosmesis outcome
Time frame: 5 years
Local Control
Time frame: 5 years
Acute Toxicity
Time frame: 90 Days
Late Toxicity
Time frame: 24 Months
Rates of Surgical Morbidity
Time frame: 5 years
Pathologic Complete Response Rates
Time frame: 5 years
Distant Disease-Free Survival
Time frame: 5 years
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 23 Sep 2026.
- Derived from this study: PubMed 41236737Rahimi A, Leitch M, Dogan B, Liu Y, Alluri P, Arbab M, Li X, Parsons DDM, Kim DWN, Wandrey N, Farr D, Seiler S, Unni N, Nguyen A, Wooldridge R, Chiu TD, Lu W, Stojadinovic S, Visak J, Nwachukwu C, Patel I, Morgan H, Bahrami S, Stein M, McArthur HL, Sahoo S, Timmerman R. Ablative Preoperative Single-Fraction Radiation Dose Escalation Among Patients With Breast Cancer: A Phase 1 Nonrandomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2543689. doi: 10.1001/jamanetworkopen.2025.43689.
- Individual participant dataSharing planned: No
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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.
Asal Rahimi, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Radiomics on MRI in people with Breast Cancer, run by University of Texas Southwestern Medical 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 14 inclusion and 9 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 23 Sep 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
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?
Reach the maximum tolerated dose (MTD) (time frame: 5 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 NCT04040569, 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 23 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.