Hypofractionated Partial Breast Irradiation in Treating Patients With Early Stage Breast Cancer

Optimizing Preventative Adjuvant Linac-Based Radiation: The OPAL Trial a Phase II/III Study of Hypofractionated Partial Breast Irradiation in Women With Early Stage Breast Cancer

This phase II trial studies how well hypofractionated partial breast irradiation works in treating patients with early stage breast cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Treating only the part of the breast where the cancer started may lead to fewer side effects than standard treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Invasive Breast Carcinoma; Early-Stage Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Ductal Breast Carcinoma In Situ; Stage 0 Breast Cancer AJCC v6 and v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Radiation: Partial Breast Irradiation

Detailed Description

PRIMARY OBJECTIVE:

I. The risk of grade 2 or higher toxicity occurring during radiation and through the 6 month post-radiation follow up visit in patients treated with Optimizing Preventative Adjuvant Linac-based Radiation (OPAL) regimen.

SECONDARY OBJECTIVES:

I. To measure patient-reported cosmetic outcome, functional status, and breast pain with the OPAL regimen at 6 months, one year, two years, three years, four years, and five years after completing the OPAL regimen.

II. To measure physician-reported and photographically-assessed cosmetic outcome at 6 months, one year, two years, three years, four years, and five years after completing the OPAL regimen and to compare this to the best performing arm of 2010-0559.

III. To determine the 5-year risk of pathologically-confirmed invasive and/or in situ ipsilateral breast tumor recurrence (IBTR) for patients with ductal breast carcinoma in situ (DCIS) and early invasive breast cancer.

IV. To determine the 5-year risk of any recurrence of breast cancer, disease-free survival, and overall survival.

V. To determine maximal late (within 5 years) toxicities using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 scale.

VI. To establish the feasibility of conducting multi-center radiation therapy trials within the MD Anderson Network.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo hypofractionated partial breast irradiation daily for 5 days. Patients may then receive 3 additional boost fractions at the discretion of the doctor.

ARM II: Patients undergo standard breast irradiation daily for 15 days. Patients may then receive 5 additional boost fractions at the discretion of the doctor.

After completion of study treatment, patients are followed up at 6 months, and at 1.5, 3.5, and 5.5 years.

• Study Type: Interventional
• Enrollment (Estimated): 928
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Benjamin D Smith; Phone Number: 713-563-2380; Email: bsmith3@mdanderson.org

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Community Cancer Center East
  • Michigan
    • Saginaw, Michigan, United States, 48602
      • Covenant Medical Center Harrison
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 07922
      • Summit Medical Group
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Voorhees, New Jersey, United States, 08043
      • MD Anderson Cancer Center at Cooper-Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Presbyterian Hospital
  • Ohio
    • Mansfield, Ohio, United States, 44903
      • OhioHealth Mansfield Hospital
  • Texas
    • Conroe, Texas, United States, 77384
      • MD Anderson in The Woodlands
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77079
      • MD Anderson West Houston
    • League City, Texas, United States, 77573
      • MD Anderson League City
    • San Antonio, Texas, United States, 78229
      • Saint Luke's Baptist Health System
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of pathologically-confirmed invasive breast cancer or ductal carcinoma in situ
• Pathologic T stage of Tis, T1, or T2 with total size of tumor =< 3 cm (this size criteria applies to both pure DCIS and invasive tumors)
• For patients with invasive breast cancer, pathologic N stage of N0, N0 (i-), or N0 (i+); pathologic staging of the axilla is not required for patients with pure DCIS
• Treatment with breast conserving surgery
• Unifocal primary tumor based on imaging and clinical assessment; microscopic multifocality is allowed
• Final surgical margins negative defined as no tumor on ink; lobular carcinoma in situ involving the final surgical margin will be disregarded
• For invasive cancers, the tumor must be estrogen receptor positive (defined as 10% or greater expression of estrogen receptor)
• If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed at least one month 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 12 weeks of the later of two dates: the final breast conserving surgical procedure or administration of the last cycle of cytotoxic chemotherapy
• Final criteria for eligibility established after simulation: The tumor bed can be readily visualized on simulation computed tomography (CT) and is localized to one quadrant or region of the breast that is amenable to partial breast irradiation

Exclusion Criteria:

• Tumor invasion of the skin including dermis, chest wall, or pectoralis musculature
• Any evidence of nodal positivity beyond pathologic stage of pN0(i+)
• Systemic chemotherapy prior to final breast conserving surgery
• Patient is pregnant or nursing
• History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast
• History of prior invasive or in situ cancer in either breast
• Current diagnosis of bilateral breast cancer
• History of lupus or scleroderma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (hypofractionated partial breast irradiation); Patients undergo hypofractionated partial breast irradiation daily for 5 days. Patients may then receive 3 additional boost fractions at the discretion of the doctor.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Radiation: Partial Breast Irradiation; Undergo hypofractionated partial breast irradiation
Active Comparator: Arm II (hypofractionated partial breast irradiation); Patients undergo standard breast irradiation daily for 15 days. Patients may then receive 5 additional boost fractions at the discretion of the doctor.	Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Partial Breast Irradiation; Undergo hypofractionated partial breast irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of grade 2 or higher toxicity	Will evaluate whether or not the risk of this outcome is higher than the risk of grade 2+ toxic events in the best performing arm of our prior clinical trial that evaluated dosing schedules of whole breast irradiation (2010-0559).	At 6 months post radiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported cosmetic outcome	Patient-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.	At 6 months, one year, two years, three years, four years, and five years after completing the optimizing preventative adjuvant linac-based radiation (OPAL) regimen
Physician-reported and photographically-assessed cosmetic outcome	Physician-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.	At 6 months, one year, two years, three years, four years, and five years after completing the OPAL regimen
Risk of pathologically-confirmed invasive and/or ipsilateral breast tumor recurrence (IBTR)	Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. IBTR will be measured from the date of treatment initiation to the date of last evaluation or IBTR. The 5-year risk of IBTR and any recurrence will be estimated along with 95% confidence intervals. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.	At 5 years
Risk of any recurrence of breast cancer	Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. Recurrence-free survival will be measured from the date of radiation treatment initiation to the earliest date of last clinic visit, date of first recurrence, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.	At 5 years
Disease free survival (DFS)	Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. DFS will be measured from date of treatment initiation to the earliest date of last clinic visit, date of progression, date of recurrence, date of metastasis, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.	At 5 years
Overall survival	Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. OS will be measured from the date of treatment initiation to the earliest date of last contact or death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.	At 5 years
Incidence of adverse events	Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4. Differences in National Cancer Institute CTCAE and Subjective, Objective, Management, Analytic (SOMA) toxicity by treatment arm will be evaluated using chi-square test or Fisher's exact test, as appropriate.	Up to 5 years
Feasibility of conducting multi-center radiation therapy trials within the MD Anderson Network	The trial will be considered feasible if >= 90% of enrolled and treated patients receive the prescribed radiation dosing per protocol without deviations.	5 years
TGF-beta analysis	For this analysis, the primary outcome is grade 2 or higher breast fibrosis measured using the Subjective, Objective, Management, Analytic/Late Effects Normal Tissue Task Force scale at the 3.5 year follow up visit. The exposure of interest is the presence of at least one copy of the C-509T allele in germline deoxyribonucleic acid (DNA). Will also conduct exploratory analyses to assess the association of TGF-beta genotype with cosmetic outcome, other PROs, and toxicities. T-test or rank-sum test will be used for continuous measures and chi-squared or Fishers exact test will be used for categorical measures.	Up to 5 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Benjamin D Smith, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD AnDERSON CANCRER CENTER WEBSITE

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2017
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Carcinoma in Situ; Breast Neoplasms; Carcinoma; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Ductal, Breast
• Other Study ID Numbers: 2016-1035 (Other Identifier: M D Anderson Cancer Center); NCI-2017-00476 (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