Shorter Course Radiation for the Treatment of Breast Cancer That Has Spread to Lymph Nodes

Hypofractionated, Comprehensive Radiation Therapy for Node-Positive Breast Cancer

The proposed study is being done to learn more about a particular dose of radiation treatment for breast cancer that is completed in a shorter amount of time than what has traditionally been used to treat breast cancer. Subjects are being asked to be in this research study because they have already had surgery for breast cancer and some cancer cells were found in their lymph nodes that drain the breast tissue.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Combination product: Adjuvant Hypofractionated Radiation

Detailed Description

Subjects who join the study will receive a shortened course of radiation treatment that will last approximately four (4) weeks, instead of the traditional six (6) week course that women have typically received in this situation. The shorter course subjects will receive is designed in a way that it is thought to be equivalent to the longer course. This shorter course has already been shown to be very safe and effective when treating breast cancer in the breast tissue only. However, because cancer cells were found in the lymph nodes that drain their breast, subjects require radiation to a larger area of their chest, armpit, and shoulder than has been completely tested with this experimental dose.

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 101 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult women (≥18 years old) with breast cancer who have undergone surgery for their primary breast tumor (either lumpectomy or mastectomy +/- reconstruction) and are confirmed to have involved lymph nodes on surgical pathology.

2. Patient who have undergone either a total mastectomy or a lumpectomy are eligible.

   Acceptable procedures for assessment of axillary nodal status at the time of surgery include:

   • axillary node dissection;
   • sentinel node biopsy alone; or
   • sentinel node biopsy followed by axillary node dissection.
3. Eligible women include AJCC (American Joint Committee on Cancer) 7th ed. Stage cN0 or cN1 subsequently staged after surgery as Stage pIB (N1mic), pIIA, pIIB, pIIIA, pIIIB, or N3a (10 or more axillary nodes) only: note that ypN0 will also be eligible if pathologic confirmation of nodal involvement was documented prior to neoadjuvant chemotherapy and the patient was found to be node-negative at the time of surgery. Note that women less than 50 years of age, women who received chemotherapy, patients staged as pN0 (i+ or mol+), and large-breasted women are eligible for enrollment.
4. The patient must have recovered from surgery with the incision completely healed and no signs of infection. If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may interfere with delivery of radiation therapy should have resolved. The patient must have an ECOG performance status of 0 or 1 (KPS >70%).
5. The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 180 days if chemotherapy is not delivered adjuvantly. If adjuvant chemotherapy was administered, the interval between the last chemotherapy treatment and randomization must be no more than 180 days.
6. Before the patient is enrolled, the consent form, including any addenda, must be signed and dated by the patient and the person who explains the study to that patient.
7. Subjects will have the ability to understand, and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. patients <18 years old
2. pregnant women
3. male patients
4. women with T4 disease, including inflammatory breast cancer
5. women who have declined or otherwise not received preceding surgery
6. women with positive margins after primary surgery
7. women with node-negative disease
8. women without histologic confirmation of nodal involvement
9. women more than 180 days out from primary breast surgery or adjuvant chemotherapy
10. patients with clinically detected or suspicious lymph node involvement not readily amenable to surgical treatment (≥cN2 disease)
11. patients with synchronous bilateral breast cancers
12. patients with prior ipsilateral thoracic or breast radiation
13. patients with distant metastatic disease (cM1) or a life expectancy of less than 5 years
14. active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma.
15. other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up.
16. patients with psychiatric or addictive disorders or other conditions that, in the opinion of the Investigator, would preclude the patient from meeting the study requirements.
17. patients with a separate non-cutaneous cancer diagnosis for which the patient has not been without evidence of disease for at least 5 years.

Note: women <50 years of age, women who received chemotherapy, pN0 (i+ or mol+), and large-breasted women are eligible for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adjuvant Hypofractionated Radiation; Adjuvant Hypofractionated Radiation (4005 cGy) will last 3-4 weeks with 15 treatments, +/- 4 additional fractions as a boost. Radiation should commence within 180 days of the date of primary surgery. Four additional fractions (a "boost" or "conedown") to areas deemed to be at particularly high risk of recurrence may be added at the end of the radiation course. Fraction size for the boost treatment will continue at 267 cGy for an additional 1068 cGy in four fractions.

Combination product: Adjuvant Hypofractionated Radiation; Hypofractionation is the delivery of radiotherapy in single daily doses greater than the 180-200 cGy. Hypofractionation, through use of larger doses per fraction and fewer total treatments, is a method of shortening overall treatment time in breast cancer therapy.; Other Names: Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE version 4.03	Any grade of 4 or 5 toxicity by CTCAE will qualify as a serious adverse event (SAE). Brachial plexopathy Grade 2 ('moderate symptoms; limiting instrumental activity of daily living (ADL)') or Grade 3 ('severe symptoms; limiting self-care ADL') and Grade 3 lymphedema ('Severe symptoms; limiting self-care ADL') and Grade 2 pneumonitis (requires steroids) will qualify as reportable adverse events (AE).	Up to 60 months
Number of participants with lymphedema severity by measuring interlimb circumference	An increase in interlimb arm circumference of at least 10% in the lower arm or the upper arm, or both, compared with the contralateral arm at the same timepoint, will be judged to be clinically significant lymphedema. Arm circumference 15 cm above the medial epicondyle (upper arms) and 15 cm below the medial epicondyle (lower arms) will be measured every 6 months, up to 60 months	Up to 60 Months
Number of participants with symptomatic rib fracture as measured by plain film or CT	Symptomatic rib fracture will be diagnosed by evidence of a correlative lesion on plain film or CT.	Up to 60 Months
Number of participants with new development of ischemic heart disease as measured by EKG	Ischemic heart disease will be measured by the new development of angina with corresponding EKG changes, or myocardial infraction.	Up to 60 Months
Number of participants reporting shoulder stiffness as measured by the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C3014) and breast-cancer module (BR23)	Reported by the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C3014) and breast-cancer module (BR23).	Up to 60 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with disease recurrence	Recurrent disease presentation within axillary lymph node levels I, II, or III. The supraclavicular region is not included in this endpoint.	Up to 60 months
Number of participants with metastasis-free survival	Measured by the time from date of enrollment to earlier of clinical detection of metastatic disease beyond the breast/chestwall and regional lymph nodes or death.	Up to 60 months
Number of participants with local-regional failure free survival	Measured by the time from date of enrollment to earlier of clinical detection of any ipsilateral recurrent disease to the breast/chestwall or regional lymph nodes (levels I, II, III, supraclavicular, and internal mammary lymph nodes) or death.	Up to 60 months
Number of participants with a change in quality of life score as measured by the EORTC QLQ-C3014 and breast-cancer module (BR23)	Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire [EORTC QLQ-C3014 and breast-cancer module (BR23)].	Up to 60 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Christine Fisher, MD, MPH, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2016
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: March 1, 2016
• First Posted (Estimated): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Radiation Therapy; Breast; Hypofractionated; Node-Positive Breast Cancer; Comprehensive Radiation Therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 15-1329.cc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes