Hypofractionated vs. Conventional Regional Nodal Radiation Therapy for Patients With Invasive Breast Cancer
Shortening Adjuvant Photon Irradiation to Reduce Edema (SAPHIRE): A Randomized Trial of Hypofractionated Versus Conventionally Fractionated Regional Nodal Irradiation for Invasive Breast Cancer
2 other identifiers
interventional
805
1 country
12
Brief Summary
To compare how often cancer recurs (comes back) after 3 weeks of radiation compared to 5 weeks of radiation in patients who receive radiation therapy delivered to the lymph nodes near the breast. The side effects that can develop during or after radiation treatment, including how often arm swelling (edema) happens, will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2017
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 19, 2016
CompletedFirst Posted
Study publicly available on registry
September 23, 2016
CompletedStudy Start
First participant enrolled
February 23, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 28, 2031
January 7, 2026
January 1, 2026
13 years
September 19, 2016
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Lymphedema rate as assessed by perometry
Will compare between patients randomized to short versus standard regional nodal irradiation (RNI). Will use a two-sided chi-squared test with a significance level of 0.05.
Up to 24 months
Secondary Outcomes (1)
Volume of affected and unaffected arm as assessed by perometry
Up to 126 months
Study Arms (2)
Arm I: Hypofractionated Regional Nodal Irradiation (RNI)
EXPERIMENTALPatients undergo hypofractionated RNI in 15 fractions 5 consecutive days a week for 3 weeks. Patients also undergo additional boost dose of radiation therapy in 5 or 7 fractions on consecutive days following completion of RNI.
Arm II: Standard Regional Nodal Irradiation (RNI)
ACTIVE COMPARATORPatients undergo standard RNI in 25 fractions 5 consecutive days a week for 5 weeks. Patients also undergo additional boost dose of radiation therapy in 5 or 7 fractions on consecutive days following completion of RNI.
Interventions
Ancillary studies
Undergo standard RNI
Undergo hypofractionated RNI
Correlative studies
Ancillary studies
Eligibility Criteria
You may qualify if:
- Radiation oncologist recommends radiation treatment to the supraclavicular and infraclavicular fossa (i.e. RNI).
- Pathologically-confirmed invasive breast cancer. If patients undergo upfront surgery, the pathologic stage must be T0-T3, N0-N2a or N3a. If patients receive neoadjuvant chemotherapy prior to surgery, the clinical stage must be T0-T3, N0-N2a or N3a. T4b disease is permitted if the patient undergoes breast conserving surgery.
- Treatment with mastectomy or segmental mastectomy and axillary evaluation (sentinel node evaluation, axillary sampling, or axillary lymph node dissection). If the patient has T0 disease, breast surgery is not required.
- Age 18 years or older.
- If enrolling on in the arm lymphedema assessment cohort, documentation of arm volume measurement by perometer prior to axillary surgery.
- If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration, and the patient must have no evidence of disease for this prior non-breast cancer.
- Patients must be enrolled on the trial within 24 weeks of the later of two dates: the final breast cancer surgical procedure or administration of the last cycle of cytotoxic chemotherapy. If after trial enrollment it is determined the patient requires additional cytotoxic chemotherapy or additional breast cancer surgery prior to radiation therapy the patient may stay on trial but the patient must start radiation therapy within 24 weeks of the final breast cancer surgical procedure or administration of the last cycle of cytotoxic chemotherapy.
- Surgeon and radiation oncologist recommend preoperative radiation therapy
- Radiation oncologist recommends radiation treatment to the supraclavicular and infraclavicular fossa (i.e. RNI).
- Pathologically-confirmed invasive breast cancer. The clinical stage must be T0-T3, N0-N3b
- Planned treatment with mastectomy and axillary evaluation (sentinel node evaluation, axillary sampling, or axillary lymph node dissection).
- Planned breast reconstruction with autologous reconstruction.
- Age 18 years or older.
- If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration, and the patient must have no evidence of disease for this prior non-breast cancer.
You may not qualify if:
- Pathologic or clinical evidence for a stage T4 breast cancer. However, T4b disease is permitted if the patient undergoes breast conserving surgery.
- Pathologic or clinical evidence for a stage N2b, N3b, or N3c breast cancer (supraclavicular, or internal mammary lymph node involvement).
- Clinical or pathologic evidence for distant metastases.
- Current diagnosis of invasive breast cancer in the contralateral breast (ductal carcinoma in situ is permitted).
- Prior diagnosis of invasive breast cancer in the contralateral breast.
- If enrolling on in the arm lymphedema assessment cohort, current diagnosis of bilateral breast cancer.
- History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast. Except those patients enrolled and treated on the PRECISE trial (MD Anderson 2017-0362).
- Patient is pregnant.
- Patients who are cognitively impaired. Subjects will undergo a brief physical exam including a brief exam to determine cognitive review.
- Pathologic or clinical evidence for a stage T4 breast cancer.
- Pathologic or clinical evidence for a stage N3c breast cancer (supraclavicular lymph node involvement).
- Clinical or pathologic evidence for distant metastases.
- Current diagnosis of invasive breast cancer in the contralateral breast (ductal carcinoma in situ is permitted).
- Prior diagnosis of invasive breast cancer in the contralateral breast.
- History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast. Except those patients enrolled and treated on the PRECISE trial (MD Anderson 2017-0362).
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)collaborator
- M.D. Anderson Cancer Centerlead
Study Sites (12)
MD Anderson Cancer Center (Banner)
Gilbert, Arizona, 85234, United States
Scripps- MD Anderson Cancer
San Diego, California, 92121, United States
MD Anderson Cancer Center (Banner)- Northern Colorado
Greeley, Colorado, 80631, United States
Baptist - MD Anderson Cancer Center
Jacksonville, Florida, 32207, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Community MD Anderson Cancer Center East
Indianapolis, Indiana, 46219, United States
Community MD Anderson Cancer Center South
Indianapolis, Indiana, 46227, United States
Community MD Anderson Cancer Center North
Indianapolis, Indiana, 49625, United States
Cooper Hospital University Medical Center
Camden, New Jersey, 08103, United States
Ohio Health
Columbus, Ohio, 43215, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
UT Health San Antonio - MD Anderson Cancer Center
San Antonio, Texas, 78229, United States
Related Publications (2)
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.
PMID: 40366003DERIVEDSchaverien 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.
PMID: 38578640DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Karen Hoffman, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2016
First Posted
September 23, 2016
Study Start
February 23, 2017
Primary Completion (Estimated)
February 28, 2030
Study Completion (Estimated)
February 28, 2031
Last Updated
January 7, 2026
Record last verified: 2026-01