Hypofractionated vs. Conventional Regional Nodal Radiation Therapy for Patients With Invasive Breast Cancer

January 9, 2024 updated by: M.D. Anderson Cancer Center

Shortening Adjuvant Photon Irradiation to Reduce Edema (SAPHIRE): A Randomized Trial of Hypofractionated Versus Conventionally Fractionated Regional Nodal Irradiation for Invasive Breast Cancer

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary Objective: To compare the risk of locoregional recurrence, defined as a cancer recurrence in the ipsilateral breast, chest wall, or regional lymph nodes (axillary levels I-III, supraclavicular, or internal mammary)

SECONDARY OBJECTIVES FOR BOTH COHORTS

  1. To compare the maximum standardized difference in arm volume between the affected arm and the unaffected arm within 24 months after completion of RNI between the two treatment arms.
  2. To compare maximal acute (within 6 weeks of treatment) and late (more than 6 weeks after treatment) skin and soft tissue toxicities using the NCI CTCAE v4.0 scale between patients assigned to short versus standard RNI.
  3. To compare patient-reported arm and shoulder function for the two treatment arms using the QuickDASH-9.
  4. To compare patient quality of life for the two treatment arms using EQ-5D-3L and PROMIS Fatigue SF 6a.
  5. To compare the peripheral blood cytokine profile at the end of radiation between patients assigned to short versus standard RNI.
  6. To evaluate the effect of the peripheral blood cytokine profile at the end of radiation on developing lymphedema. (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health)
  7. To evaluate the effect of homocysteine levels prior to radiation on developing lymphedema. (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health)
  8. To evaluate time to distant metastasis, disease-free survival and overall survival for patients assigned to short versus standard RNI.
  9. To evaluate the effect of lipid profiles prior to radiation on acute toxicity, patient reported outcomes, and the time to locoregional recurrence. (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health)
  10. To evaluate if DNA repair capacity contributes to the presence of acute radiation related toxicity and patient-reported quality of life decrements including fatigue and arm and shoulder symptoms. (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health)
  11. To evaluate changes in echocardiography global longitudinal strain measurements and cardiac serum biomarkers, based on measurements performed before and after RT, in patients assigned to short versus standard RNI. (optional procedure for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health)
  12. In a separate cohort of 50 patients who will receive RNI before surgery, to collect information on number of patients developing lymphedema within 24 months of RNI on reconstructive complications, and on patient reported quality of life, in those assigned to short versus standard RNI. Participating Cancer Network Sites, or Orlando Health, are not participating in this cohort.
  13. To evaluate patient-reported financial burdens using the Economic Strain and Resilience in Cancer- Financial Well- Being instrument.
  14. To determine whether radiation therapy induces de novo detectable clonal hematopoiesis mutations or alters the genetic landscape of existing clonal hematopoiesis mutations (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health).
  15. To determine whether radiation therapy or chemotherapy among individuals with pre- and/or post-treatment clonal hematopoiesis mutations is associated with adverse treatment effects and worse oncologic outcomes (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients, or Orlando Health).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo hypofractionated RNI in 15 fractions 5 consecutive days a week for 3 weeks.

ARM II: Patients undergo standard RNI in 25 fractions 5 consecutive days a week for 5 weeks.

In both arms, patients undergo additional boost dose of radiation therapy in 5 or 7 fractions on consecutive days following completion of RNI.

PATIENT EVALUATION: Patients participating in the trial will have their arm measured prior to radiation, during the final week of radiation and when they return for follow up visits. Patients will be checked for any arm swelling that may develop. Patients will also fill out questionnaires before treatment and when they return for follow up visits. Patients return 3 and 6 months after radiation, then every 6 months through two and a half years after radiation and then on a yearly basis until ten and a half years after finishing radiation. At some of the follow up visits, we measure arm volume and ask participants to complete questionnaires.

Study Type

Interventional

Enrollment (Estimated)

985

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Recruiting
        • MD Anderson Cancer Center (Banner)
        • Contact:
        • Principal Investigator:
          • Mohamed Khan, MD
    • California
      • San Diego, California, United States, 92121
        • Recruiting
        • Scripps- MD Anderson Cancer
        • Contact:
        • Principal Investigator:
          • Ray Lin, MD
    • Colorado
      • Greeley, Colorado, United States, 80631
        • Recruiting
        • MD Anderson Cancer Center (Banner)- Northern Colorado
        • Contact:
        • Principal Investigator:
          • Supriya Jain, MD
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Baptist - MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Cynthia Anderson, MD
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health Cancer Institute
        • Contact:
        • Principal Investigator:
          • Cameron Swanick, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46219
        • Recruiting
        • Community MD Anderson Cancer Center East
        • Contact:
        • Principal Investigator:
          • Daniel Weed, M D
      • Indianapolis, Indiana, United States, 46227
        • Recruiting
        • Community MD Anderson Cancer Center South
        • Contact:
        • Principal Investigator:
          • Daniel Weed, M D
      • Indianapolis, Indiana, United States, 49625
        • Recruiting
        • Community MD Anderson Cancer Center North
        • Contact:
        • Principal Investigator:
          • Daniel Weed, M D
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Recruiting
        • Cooper Hospital University Medical Center
        • Contact:
        • Principal Investigator:
          • Stuti Ahlawat, MD
    • Ohio
      • Columbus, Ohio, United States, 43215
        • Recruiting
        • Ohio Health
        • Contact:
        • Principal Investigator:
          • Virginia Davolitsis, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Contact:
          • Karen E. Hoffman, MD
          • Phone Number: 713-563-2331
        • Principal Investigator:
          • Karen E. Hoffman, MD
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • UT Health San Antonio - MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Dalwadi Shraddha, M D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria, if receiving postoperative radiation therapy

  • 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.

Inclusion Criteria, if receiving preoperative radiation therapy

  • 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.

Exclusion Criteria, if receiving postoperative radiation therapy

  • 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.

Exclusion Criteria, if receiving preoperative radiation therapy

  • 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).
  • Patient is pregnant.
  • Patients who are cognitively impaired. Subjects will undergo a brief physical exam including a brief exam to determine cognitive review.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I: Hypofractionated Regional Nodal Irradiation (RNI)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Radiation: Hypofractionated Radiation Therapy
Undergo hypofractionated RNI
Other Names:
  • Hypofractionated Radiotherapy
  • hypofractionation
Active Comparator: Arm II: Standard Regional Nodal Irradiation (RNI)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Radiation: Radiation Therapy
Undergo standard RNI
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Radiation
  • Radiotherapeutics
  • RT
  • Therapy, Radiation
  • irradiation
  • RADIOTHERAPY

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lymphedema rate as assessed by perometry
Time Frame: Up to 24 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volume of affected and unaffected arm as assessed by perometry
Time Frame: Up to 126 months
The Shapiro-Wilk test will be used to objectively assess the normality of the data and these findings will be visually confirmed by inspecting normal probability quantile-quantile plots. If the data are not normally distributed, a normalizing transformation before using t-test or a non-parametric method such as the Wilcoxon rank sum test to compare the standardized difference between the two arms at each time point may be used.
Up to 126 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Karen Hoffman, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2017

Primary Completion (Estimated)

February 28, 2030

Study Completion (Estimated)

February 28, 2031

Study Registration Dates

First Submitted

September 19, 2016

First Submitted That Met QC Criteria

September 22, 2016

First Posted (Estimated)

September 23, 2016

Study Record Updates

Last Update Posted (Actual)

January 10, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-0142 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2016-01941 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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