Breast CancerPhase 2NCT07076485
Shortening Adjuvant Photon and Proton Irradiation (SAPPHIRe-II): A 4 Cohort, Randomized, Phase II Multi-center Trial Evaluating Shorter Schedules of Adjuvant Regional Nodal Irradiation Among Women and Men With Node-positive and High-risk Node-negative Invasive Breast Cancer
A Phase 2 study testing Ultrahypofractionated Radiation and Moderately Hypofractionated Radiation in people with Breast Cancer, run by M.D. Anderson Cancer Center at 5 sites in United States.
Trial summary
To learn about the effects of shorter RNI regimens in patients with breast cance who have had a lumpectomy or mastectomy and who are at higher risk for lower risk for the disease returning. 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?
- Ultrahypofractionated Radiation and Moderately Hypofractionated Radiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 768 participants
- Where
- 5 sitesUnited States
- Study dates
- 19 Aug 2025to 1 Jan 2031
- Phase
- Phase 2
- 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
- Eligibility Criteria Applicable to All Cohorts
- Histologically confirmed invasive breast cancer (nodal involvement from presumed invasive breast cancer in the setting of occult breast cancer is sufficient to meet this criteria)
- 1. Regional nodal irradiation recommended by treating radiation oncologist. 2 Negative final surgical margins. 3 No more than 12 weeks have elapsed since final breast/lymph node surgery for patients treated with surgery alone or neoadjuvant chemotherapy. No more than 12 weeks have elapsed since final cytotoxic chemotherapy for patients who received adjuvant chemotherapy. 5. Age ≥18 years. Because breast cancer is exceedingly rare in patients < 18 years of age, children are excluded from this study. 6. Patients with a prior or concurrent malignancy are eligible provided that the natural history and treatment of the prior or concurrent malignancy does not interfere with the safety or efficacy assessment of the investigational radiation regimen used in this trial. 7. Ability to understand and the willingness to sign a written informed consent document. 8. Concurrent enrollment on other observational, translational, or therapeutic studies is allowed provided there is no direct conflict between the other protocol and the radiation regimen proscribed in this trial.
- Eligibility Criteria for the Low-Risk Lumpectomy Cohort
- For patients treated with upfront surgery, pathologic stage pT0-T4b N0-N3a breast cancer without infraclavicular or internal mammary nodal involvement.
- For patients treated with neoadjuvant chemotherapy, clinical stage cT0-T4b N0-N2a breast cancer.
Show all 36Show fewer
- Treated with lumpectomy (or axillary surgery only in the case of occult primary breast cancer)
- No nodal boost recommended by the treating radiation oncologist.
- Eligibility Criteria for the High-Risk Lumpectomy Cohort
- Treated with neoadjuvant chemotherapy
- Clinical stage cT0-T4b N1-N3a/b/c
- Treated with lumpectomy (or axillary surgery only in the case of occult primary breast cancer)
- Nodal boost recommended by the treating radiation oncologist.
- Eligibility Criteria for the Low-Risk Mastectomy Cohort
- For patients treated with upfront surgery, pathologic stage T0-T2 N0-N2a
- For patients treated with neoadjuvant chemotherapy, clinical stage T0-T3 N0- N2a
- For patients treated with neoadjuvant chemotherapy, residual cellularity of primary tumor ≤ 20%.
- Treated with mastectomy
- Negative surgical margins ≥ 2 mm.
- No or only focal lymphovascular space invasion.
- Age ≥ 40 years
- Chest wall boost NOT recommended by treating radiation oncologist.
- Eligibility Criteria for High-Risk Mastectomy Cohort
- For patients treated with upfront surgery, pathologic stage T0-T4d N0-N3c
- For patients treated with neoadjuvant chemotherapy, clinical stage T0-T4d N0- N3c
- Treated with mastectomy
- Chest wall boost and/or nodal boost recommended by treating radiation oncologist
- Pregnancy Status (applicable to all cohorts)
- Therapeutic radiation is known to be teratogenic. As a result, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of radiation treatment. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the radiation therapy course is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Men treated or enrolled on this protocol must also agree to use adequate contraception during the radiation treatment course.
- Pregnancy testing at the time of study enrollment is not required of women who enroll. However, all patients must comply with the Institutional Pregnancy Assessment Policy (# CLN1114) which requires pregnancy testing within 7 days prior to simulation.
Who cannot join
- History of therapeutic radiation overlapping with the index breast or nodal basins that require radiation therapy.
- History of scleroderma
- Pregnant women are excluded from this study because ionizing radiation has the potential for teratogenic or abortifacient effects.
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Benjamin Smith, MD, 713-563-2380, bsmith3@mdanderson.org
Benjamin Smith, MD
- Recruiting
Baptist MD Anderson
Jacksonville, Florida, 32207
Cynthia Anderson, MD, Cynthia.Anderson@bmcjax.com
Cynthia Anderson, MD
- Recruiting
Banner MD Anderson Northern Colorado
Loveland, Colorado, 80538
Supriya Jain, MD, supriya.jain@bannerhealth.com
Supriya Jain, MD
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Shraddha Dalwadi, MD, MBA, 210-567-1203, dalwadi@uthscsa.edu
Shraddha Dalwadi, MD, MBA
- Recruiting
Cooper Hospital University Medical Center
Voorhees Township, New Jersey, 08103
Anthony Dragun, MD, 855-632-2667, dragun-anthony@CooperHealth.edu
Anthony Dragun, MD
About this study
To learn about the effects of shorter RNI regimens in patients with breast cance who have had a lumpectomy or mastectomy and who are at higher risk for lower risk for the disease returning.
Read the detailed description
Primary Objective:
To compare the occurrence of any grade 2 or higher NCI CTCAE toxicity from start of RNI through 18 months follow up by treatment arm for each of the four randomized cohorts (low-risk lumpectomy, low-risk mastectomy, high-risk lumpectomy, high-risk mastectomy).
Secondary Objectives:
To compare treatment toxicity, local-regional control, disease-free survival, and overall survival by treatment arm for each of the four randomized cohorts.
To compare patient-reported outcomes including cosmetic satisfaction, physical wellbeing, lymphatic function, and financial toxicity by treatment arm for each of the four randomized cohorts.
To compare photographic outcome of the treated breast or reconstructed breast by treatment arm for each of the four randomized cohorts.
To evaluate and compare radiation treatment plans by treatment arm for each of the four randomized cohorts, including target coverage, dose to organs at risk, dose homogeneity, and low-dose scatter.
To compare biometric data before, during, and after radiation collected by patients' personal Apple Watches.
- Conditions
- Breast Cancer
- Being tested
- Ultrahypofractionated Radiation, Moderately Hypofractionated Radiation
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrahypofractionated RadiationRadiation
Given by infusion
Moderately Hypofractionated RadiationRadiation
Given by infusion
| Study group | Role | What they receive |
|---|---|---|
| High-Risk Lumpectomy Cohort Arm 1: Moderately Hypofractionated Breast+RNI with SIB | Experimental | Not described Receives: Radiation: Moderately Hypofractionated Radiation |
| High-Risk Lumpectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI with Sequential Boost | Other | Not described Receives: Radiation: Moderately Hypofractionated Radiation |
| High-Risk Mastectomy Cohort Arm 1: Moderately Hypofractionated Chest Wall+RNI with SIB | Experimental | Not described Receives: Radiation: Moderately Hypofractionated Radiation |
| High-Risk Mastectomy Cohort Arm 2: Moderately Hypofractionated Chest Wall+RNI with Sequential Boost | Other | Not described Receives: Radiation: Moderately Hypofractionated Radiation |
| Low-Risk Lumpectomy Cohort Arm 1: Ultrahypofractionated Breast+RNI with SIB | Experimental | Not described Receives: Radiation: Ultrahypofractionated Radiation |
| Low-Risk Lumpectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI with SIB | Other | Not described Receives: Radiation: Moderately Hypofractionated Radiation |
| Low-Risk Mastectomy Cohort Arm 1: Ultrahypofractionated Chest Wall+RNI | Experimental | Not described Receives: Radiation: Ultrahypofractionated Radiation |
| Low-Risk Mastectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI | Other | Not described Receives: Radiation: Moderately Hypofractionated Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events (AEs)
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 posted22 Jul 2025
- Study start19 Aug 2025
- Primary completion1 Jan 2029 (estimated)
- Study completion1 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 768 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin Smith, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07076485
- Sponsor's protocol ID
- 2025-0779
- Other IDs
- NCI-2025-05190
- Status last verified
- Aug 2026
- First submitted
- 15 Jul 2025
- Last updated
- 2 Sep 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 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Shortening Adjuvant Photon and Proton Irradiation (SAPPHIRe-II): A 4 Cohort, Randomized, Phase II Multi-center Trial Evaluating Shorter Schedules of Adjuvant Regional Nodal Irradiation Among Women and Men With Node-positive and High-risk Node-negative Invasive Breast Cancer
- ClinicalTrials.gov ID
- NCT07076485
- Acronym / sponsor ID
- 2025-0779
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 768 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 19 Aug 2025 (actual)
- Primary completion
- 1 Jan 2029 (estimated)
- Study completion
- 1 Jan 2031 (estimated)
- First posted
- 22 Jul 2025 (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 learn about the effects of shorter RNI regimens in patients with breast cance who have had a lumpectomy or mastectomy and who are at higher risk for lower risk for the disease returning.
Detailed description
Primary Objective:
To compare the occurrence of any grade 2 or higher NCI CTCAE toxicity from start of RNI through 18 months follow up by treatment arm for each of the four randomized cohorts (low-risk lumpectomy, low-risk mastectomy, high-risk lumpectomy, high-risk mastectomy).
Secondary Objectives:
To compare treatment toxicity, local-regional control, disease-free survival, and overall survival by treatment arm for each of the four randomized cohorts.
To compare patient-reported outcomes including cosmetic satisfaction, physical wellbeing, lymphatic function, and financial toxicity by treatment arm for each of the four randomized cohorts.
To compare photographic outcome of the treated breast or reconstructed breast by treatment arm for each of the four randomized cohorts.
To evaluate and compare radiation treatment plans by treatment arm for each of the four randomized cohorts, including target coverage, dose to organs at risk, dose homogeneity, and low-dose scatter.
To compare biometric data before, during, and after radiation collected by patients' personal Apple Watches.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| High-Risk Lumpectomy Cohort Arm 1: Moderately Hypofractionated Breast+RNI with SIB | Experimental | Radiation: Moderately Hypofractionated Radiation |
| High-Risk Lumpectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI with Sequential Boost | Other | Radiation: Moderately Hypofractionated Radiation |
| High-Risk Mastectomy Cohort Arm 1: Moderately Hypofractionated Chest Wall+RNI with SIB | Experimental | Radiation: Moderately Hypofractionated Radiation |
| High-Risk Mastectomy Cohort Arm 2: Moderately Hypofractionated Chest Wall+RNI with Sequential Boost | Other | Radiation: Moderately Hypofractionated Radiation |
| Low-Risk Lumpectomy Cohort Arm 1: Ultrahypofractionated Breast+RNI with SIB | Experimental | Radiation: Ultrahypofractionated Radiation |
| Low-Risk Lumpectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI with SIB | Other | Radiation: Moderately Hypofractionated Radiation |
| Low-Risk Mastectomy Cohort Arm 1: Ultrahypofractionated Chest Wall+RNI | Experimental | Radiation: Ultrahypofractionated Radiation |
| Low-Risk Mastectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI | Other | Radiation: Moderately Hypofractionated Radiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Eligibility Criteria Applicable to All Cohorts
- Histologically confirmed invasive breast cancer (nodal involvement from presumed invasive breast cancer in the setting of occult breast cancer is sufficient to meet this criteria)
- 1. Regional nodal irradiation recommended by treating radiation oncologist. 2 Negative final surgical margins. 3 No more than 12 weeks have elapsed since final breast/lymph node surgery for patients treated with surgery alone or neoadjuvant chemotherapy. No more than 12 weeks have elapsed since final cytotoxic chemotherapy for patients who received adjuvant chemotherapy. 5. Age ≥18 years. Because breast cancer is exceedingly rare in patients < 18 years of age, children are excluded from this study. 6. Patients with a prior or concurrent malignancy are eligible provided that the natural history and treatment of the prior or concurrent malignancy does not interfere with the safety or efficacy assessment of the investigational radiation regimen used in this trial. 7. Ability to understand and the willingness to sign a written informed consent document. 8. Concurrent enrollment on other observational, translational, or therapeutic studies is allowed provided there is no direct conflict between the other protocol and the radiation regimen proscribed in this trial.
- Eligibility Criteria for the Low-Risk Lumpectomy Cohort
- For patients treated with upfront surgery, pathologic stage pT0-T4b N0-N3a breast cancer without infraclavicular or internal mammary nodal involvement.
Key exclusion criteria (4 listed)
- History of therapeutic radiation overlapping with the index breast or nodal basins that require radiation therapy.
- History of scleroderma
- Pregnant women are excluded from this study because ionizing radiation has the potential for teratogenic or abortifacient effects.
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| Ultrahypofractionated RadiationGiven by infusion | Radiation | Low-Risk Lumpectomy Cohort Arm 1: Ultrahypofractionated Breast+RNI with SIB, Low-Risk Mastectomy Cohort Arm 1: Ultrahypofractionated Chest Wall+RNI |
| Moderately Hypofractionated RadiationGiven by infusion | Radiation | High-Risk Lumpectomy Cohort Arm 1: Moderately Hypofractionated Breast+RNI with SIB, High-Risk Lumpectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI with Sequential Boost, High-Risk Mastectomy Cohort Arm 1: Moderately Hypofractionated Chest Wall+RNI with SIB, High-Risk Mastectomy Cohort Arm 2: Moderately Hypofractionated Chest Wall+RNI with Sequential Boost, Low-Risk Lumpectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI with SIB, Low-Risk Mastectomy Cohort Arm 2: Moderately Hypofractionated Breast+RNI |
Primary outcome
Safety and Adverse Events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
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 2 Sep 2026.
- MD Anderson Cancer Center WebsiteLink 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 Smith, MD principal investigator
M.D. Anderson Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ultrahypofractionated Radiation and Moderately Hypofractionated Radiation in people with Breast Cancer, run by M.D. Anderson Cancer Center at 5 sites 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 36 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 2 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 5 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 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?
Safety and Adverse Events (AEs) (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?
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 2 Sep 2026.