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

Phase 2

Active, not recruiting

Conditions: Breast Cancer

Interventions: Combination Product: Adjuvant Hypofractionated Radiation

Registration Number: NCT02700386

Lead Sponsor: University of Colorado, Denver

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Female

Target Recruitment: 108

Inclusion Criteria

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.
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.
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.
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%).
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.
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.
Subjects will have the ability to understand, and the willingness to sign a written informed consent document.

Exclusion Criteria

patients <18 years old
pregnant women
male patients
women with T4 disease, including inflammatory breast cancer
women who have declined or otherwise not received preceding surgery
women with positive margins after primary surgery
women with node-negative disease
women without histologic confirmation of nodal involvement
women more than 180 days out from primary breast surgery or adjuvant chemotherapy
patients with clinically detected or suspicious lymph node involvement not readily amenable to surgical treatment (≥cN2 disease)
patients with synchronous bilateral breast cancers
patients with prior ipsilateral thoracic or breast radiation
patients with distant metastatic disease (cM1) or a life expectancy of less than 5 years
active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma.
other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up.
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.
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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adjuvant Hypofractionated Radiation	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With at Least One Treatment-related Adverse Event of Interest	12 months and 36 months	The composite endpoint is "yes" for a given patient if that patient experienced at least one of six component adverse events: lymphedema, shoulder ROM impairment, cardiac ischemia, symptomatic rib fracture, brachial plexopathy Grade 2 ('moderate symptoms; limiting instrumental activity of daily living (ADL)') or Grade 3 ('severe symptoms; limiting self-care ADL'), or Grade 2 pneumonitis (requires steroids). AEs were assessed by CTCAE version 4.03.
Number of Participants With Grade 2 or Higher Brachial Plexopathy	12 months and 36 months	Number of patients who experience brachial plexopathy as an adverse event at Grade 2 or higher as assessed by CTCAE v 4.03.
Number of Participants With Lymphedema Severity by Measuring Interlimb Circumference	12 months and 36 months	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 assessed at 12 months and at 36 months.
Number of Participants With Symptomatic Rib Fracture as Measured by Plain Film or CT	12 months and 36 months	Symptomatic rib fracture will be diagnosed by evidence of a correlative lesion on plain film or CT.
Number of Participants With New Development of Ischemic Heart Disease as Measured by EKG	12 months and 36 months	Ischemic heart disease will be measured by the new development of angina with corresponding EKG changes, or myocardial infraction.
Number of Participants Reporting Shoulder Stiffness as Measured by the EORTC QLQ-BR23	12 months and 36 months	Shoulder stiffness severity is assessed using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire breast cancer module (EORTC QLQ-BR23). It is assessed based on patient response to the questionnaire item, "During the past week, was it difficult to raise your arm or to move it sideways?", which is scored from 1 to 4 with 1 being "not at all" and 4 being "very much". Shoulder stiffness is identified in a patient when their response to that question is 3 or 4 AND if their response increased numerically from their response on day 1.
Number of Participants With Grade 2 or Higher Pneumonitis	12 months and 36 months	Number of patients who experience pneumonitis as an adverse event at Grade 2 or higher as assessed by CTCAE v 4.03.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Local-regional Failure Free Survival	12 months and 36 months	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.
Number of Participants With Metastasis-free Survival	12 months and 36 months	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.
Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-BR23	Baseline to 1 year post-intervention	Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire breast cancer module \[EORTC QLQ-BR23 V1\]. Summary scores and missing data handling were performed according to the EORTC QLQ-BR23. The minimum score is 0, and the maximum score is 100. A higher score is a better outcome. A change in score is defined as a score increase of at least 10 points from baseline.
Number of Participants With a Change in Quality of Life Score as Measured by the EORTC QLQ-C30	From baseline up to 12 months	Patient's quality of life from pre-treatment to post-treatment, reported by the quality of life questionnaire \[EORTC QLQ-C30 V1\]. Summary scores and missing data handling were performed according to the EORTC QLQ-C30. The minimum score is 0, and the maximum score is 100. A higher score is a better outcome. A change in score is defined as a score increase of at least 10 points at the 12 month mark compared to baseline.
Number of Participants With Disease Recurrence	Up to 60 months	Recurrent disease presentation within axillary lymph node levels I, II, or III. The supraclavicular region is not included in this endpoint.

Trial Locations

Locations (3): Poudre Valley Hospital
🇺🇸
Fort Collins, Colorado, United States
Memorial Hospital
🇺🇸
Colorado Springs, Colorado, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States