Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases

This phase I trial studies the side effects and the best dose of stereotactic body radiation therapy in treating patients with breast cancer, non-small cell lung cancer, or prostate cancer that has spread to other parts of the body. Stereotactic body radiation therapy delivers fewer, tightly-focused, high doses of radiation therapy to all known sites of cancer in the body while minimizing radiation exposure of surrounding normal tissue.

Study Overview

• Status: Completed
• Conditions: Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer; Prostate Adenocarcinoma; Stage IV Breast Cancer; Recurrent Breast Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer; Male Breast Carcinoma
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT)

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the recommended stereotactic body radiation therapy (SBRT) dose for each of the metastatic locations being treated given the individual and overlapping fields when multiple metastases are treated with SBRT in a national clinical trials network setting.

SECONDARY OBJECTIVES:

I. To estimate rates of >= grade 3 Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4.0 adverse events other than a dose-limiting toxicity (DLT) which is possibly, probably, or definitely related to treatment and which occurs within 6 months from the start of SBRT to multiple metastases.

II. To estimate the rates of long-term adverse events occurring up to 2 years from the end of SBRT.

III. To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout radiation therapy processes, including imaging, simulation, patient immobilization, target and critical structure definition, treatment planning, image guidance and delivery.

OUTLINE:

Patients undergo 3-5 fractions of image-guided stereotactic body radiation therapy to all existing metastases over 1-3 weeks with at least 40 hours between treatments for an individual metastasis.

After completion of study treatment, patients are followed up at 35-45 days and then every 3 months for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM - Centre Hospitalier de l'Universite de Montreal
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Arizona Center for Cancer Care-Peoria
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Swansea, Illinois, United States, 62226
      • Southwest Illinois Health Services LLP
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bel Air, Maryland, United States, 21014
      • UM Upper Chesapeake Medical Center
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Clarkston, Michigan, United States, 48346
      • GenesisCare USA - Clarkston
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Farmington Hills, Michigan, United States, 48334
      • GenesisCare USA - Farmington Hills
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute-Macomb
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute-Northern Michigan
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Troy, Michigan, United States, 48098
      • GenesisCare USA - Troy
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Mount Laurel, New Jersey, United States, 08054
      • Cooper CyberKnife Center
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Voorhees Township, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
  • Pennsylvania
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
  • Utah
    • Ogden, Utah, United States, 84405
      • Ogden Regional Medical Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Administration Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Metastatic breast cancer (MBC) OR metastatic non-small cell lung cancer (NSCLC) OR metastatic adenocarcinoma of the prostate; the sites of allowed metastases are: peripheral lung, central lung, mediastinal/cervical lymph node, liver, spinal/paraspinal, osseous, and abdominal-pelvic

  • NOTE: after the required number of evaluable patients have been accrued for a given dose level, the accrual for that metastatic location will be temporarily suspended while the safety of that dose level is assessed; a patient can only be entered onto the trial if all of their metastatic locations are open to accrual (e.g. if central lung is temporarily suspended for safety assessment and the patient has a central lung metastases, regardless of other metastases, they cannot enroll until the safety of dose to central lung is determined)
• Primary tumor site without progression at registration
• All metastases not resected must be amenable to SBRT

• The patient must meet ONE of the three following criteria:

  • 3-4 radiographically distinct metastases of any distribution in the allowed anatomical sites OR
  • 2 radiographically distinct metastases that must be anatomically close (i.e., with less than or equal to 5 cm of normal tissue between them) OR
  • 3 or 4 distinct metastasis, 2 or 3 to be treated with SBRT and the other (s) having been surgically removed
• Evaluation by a radiation oncologist within 45 days prior to study registration
• Evaluation by a medical oncologist within 45 days prior to study registration

• The following imaging workup to document metastases within 45 days prior to study registration:

  • Computed tomography (CT) scans of the chest, abdomen and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT
• History/physical examination within 45 days prior to study registration
• Zubrod performance status =< 2 within 45 days prior to study registration
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 500 cells/mm^3
• Platelets >= 50,000 /mm^3
• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• If liver metastases present, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be < 3 x upper limit of normal (ULN)
• Patient must provide study specific informed consent prior to study entry
• For females of child-bearing potential, negative serum/urine pregnancy test within 14 days prior to study registration

Exclusion Criteria:

• Progression of primary tumor site (breast, prostate, or lung) at time of registration
• Metastases with indistinct borders making targeting not feasible
• Known brain metastases
• Prior palliative radiotherapy to metastases

• Metastases located within 3 cm of the previously irradiated structures:

  • Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)
  • Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
  • Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)
  • Brain stem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
  • Whole lung previously irradiated with prior volume 20 Gy (V20Gy) > 30% (delivered in =< 3 Gy/fraction)
  • Primary tumor irradiated with SBRT
  • Metastasis irradiated with SBRT

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
  • Transmural myocardial infarction within the last 6 months prior to registration
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
  • Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
  • Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD) 4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
  • End-stage renal disease (i.e., on dialysis or dialysis has been recommended)
• Pregnancy or women of childbearing potential not willing/able to use medically acceptable forms of contraception during protocol treatment or for at least 6 months following treatment

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: Stereotactic Body Radiation Therapy (SBRT); Patients undergo 3-5 fractions of image-guided stereotactic body radiation therapy to all existing metastases over 1-3 weeks with at least 40 hours between treatments for an individual metastasis.	Radiation: Stereotactic Body Radiation Therapy (SBRT); Undergo SBRT; Other Names: SBRT; stereotactic radiosurgery; Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery; Stereotactic Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT) scored according to the National Cancer Institute (NCI) CTCAE version 4.0 for each of 7 metastatic locations when multiple metastases are treated with SBRT	Adverse events outlined by metastatic location (full detail in protocol) reported as being probably or definitely related to protocol treatment.	Within 6 months from the start of treatment; for each of the 7 metastatic locations, analysis occurs after 6 evaluable patients have been followed for a minimum of 6 months from the start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of long-term adverse events, scored according to the NCI CTCAE v. 4.0	Adverse events reported as being possibly, probably, or definitely related to protocol treatment.	Up to 2 years from end of treatment; analysis occurs after all patients have been potentially followed for 2 years from registration
Rates of >= grade 3 adverse events, scored according to NCI CTCAE v. 4.0	Adverse events (other than DLTs) reported as being possibly, probably, or definitely related to protocol treatment.	Within 6 months from the start of treatment; analysis occurs after all patients have been followed for a minimum of 6 months from the start of treatment

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven Chmura, NRG Oncology

Publications and helpful links

General Publications

• Chmura S, Winter KA, Robinson C, Pisansky TM, Borges V, Al-Hallaq H, Matuszak M, Park SS, Yi S, Hasan Y, Bazan J, Wong P, Yoon HA, Horton J, Gan G, Milano MT, Sigurdson ER, Moughan J, Salama JK, White J. Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial. JAMA Oncol. 2021 Jun 1;7(6):845-852. doi: 10.1001/jamaoncol.2021.0687.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimated): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms, Male; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: NRG-BR001 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); U10CA021661 (U.S. NIH Grant/Contract); NCI-2014-00702 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Drug and device information, study documents

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