Testing Whether Treating Breast Cancer Metastases With Surgery or High-Dose Radiation Improves Survival

January 9, 2024 updated by: NRG Oncology

A Phase IIR/III Trial of Standard of Care Therapy With or Without Stereotactic Body Radiotherapy (SBRT) and/or Surgical Ablation for Newly Oligometastatic Breast Cancer

This randomized phase II/III trial studies how well standard of care therapy with stereotactic radiosurgery and/or surgery works and compares it to standard of care therapy alone in treating patients with breast cancer that has spread to one or two locations in the body (limited metastatic) that are previously untreated. Standard of care therapy comprising chemotherapy, hormonal therapy, biological therapy, and others may help stop the spread of tumor cells. Radiation therapy and/or surgery is usually only given with standard of care therapy to relieve pain; however, in patients with limited metastatic breast cancer, stereotactic radiosurgery, also known as stereotactic body radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue and surgery may be able to effectively remove the metastatic tumor cells. It is not yet known whether standard of care therapy is more effective with stereotactic radiosurgery and/or surgery in treating limited metastatic breast cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Phase II: To determine whether ablation [through stereotactic body radiation therapy (SBRT) (stereotactic radiosurgery) and/or surgical resection of all known metastases] in oligometastatic breast cancer patients provides a sufficient signal for improved progression-free survival (PFS) to warrant full accrual to the Phase III portion of the trial.

II. Phase III: To determine whether ablation (through SBRT and/or surgical resection of all known metastases) in oligometastatic breast cancer patients significantly improves overall survival (OS).

SECONDARY OBJECTIVES:

I. To evaluate treated metastasis control according to tumor receptor status [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)], use of chemotherapy, surgery versus (vs.) ablative therapy, and number of metastases.

II. To evaluate whether the addition of ablative metastasis directed therapy significantly reduces the number of distant recurrences (new metastases) in patients who progress according to tumor receptor status (ER, PR, HER-2); use of chemotherapy, and number of metastases.

III. To evaluate adverse events in patients who receive ablative metastasis-directed therapy to all known metastases in addition to standard medical therapy compared with those treated with standard medical therapy alone.

EXPLORATORY OBJECTIVE:

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

TRANSLATIONAL RESEARCH OBJECTIVES:

I. To determine whether < 5 circulating tumor cells (CTCs) (per 7.5 ml of blood) is an independent prognostic (outcome) marker for improved PFS and OS in oligometastatic breast cancer.

II. To determine whether < 5 CTCs (per 7.5 ml of blood) is an independent predictive (response to therapy) marker for improved PFS and OS in oligometastatic breast cancer.

III. To determine whether eliminating CTCs (0/7.5 ml of blood in patients with at least 2 CTCs at registration) is both a prognostic and predictive marker for improved PFS and OS.

IV. To evaluate the prognostic and predictive properties of CTC count as a continuous measure of PFS and OS.

V. To store material for retrospective analysis of circulating tumor deoxyribonucleic acid (ctDNA).

VI. To store material for retrospective analysis of circulating micro-ribonucleic acid (RNA).

Study Type

Interventional

Enrollment (Actual)

129

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

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

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital and Cancer Center-General Campus
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H3H 2R9
        • The Research Institute of the McGill University Health Centre (MUHC)
      • Montreal, Quebec, Canada, H2L 4M1
        • CHUM - Hopital Notre-Dame
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill University Department of Oncology
      • Montreal, Quebec, Canada, H2X 3E4
        • CHUM - Centre Hospitalier de L'Universite de Montreal
  • Korea, Republic of
      • Seoul, Korea, Republic of, 120-752
        • Yonsei University Health System-Severance Hospital
  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11211
        • King Faisal Specialist Hospital and Research Centre
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
    • Arizona
      • Goodyear, Arizona, United States, 85338
        • CTCA at Western Regional Medical Center
      • Peoria, Arizona, United States, 85381
        • Arizona Center for Cancer Care-Peoria
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
    • California
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Medical Center-Herrick Campus
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Roseville, California, United States, 95678
        • The Permanente Medical Group-Roseville Radiation Oncology
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92134
        • Naval Medical Center -San Diego
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente Cancer Treatment Center
      • Stockton, California, United States, 95204
        • Saint Joseph's Medical Center
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Colorado Springs, Colorado, United States, 80909
        • UCHealth Memorial Hospital Central
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Loveland, Colorado, United States, 80539
        • McKee Medical Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Science Center - Gainesville
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Orlando, Florida, United States, 32806
        • Orlando Health Cancer Institute
      • Pembroke Pines, Florida, United States, 33028
        • Memorial Hospital West
    • 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, 30342
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30309
        • Piedmont Hospital
      • Columbus, Georgia, United States, 31904
        • John B Amos Cancer Center
      • Newnan, Georgia, United States, 30265
        • CTCA at Southeastern Regional Medical Center
      • Thomasville, Georgia, United States, 31792
        • Lewis Hall Singletary Oncology Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61636
        • Methodist Medical Center of Illinois
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Swansea, Illinois, United States, 62226
        • Southwest Illinois Health Services LLP
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
      • Zion, Illinois, United States, 60099
        • Midwestern Regional Medical Center
    • Indiana
      • Anderson, Indiana, United States, 46016
        • Ascension Saint Vincent Anderson
      • Fort Wayne, Indiana, United States, 46805
        • Parkview Hospital Randallia
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Regional Medical Center
      • Muncie, Indiana, United States, 47303
        • IU Health Ball Memorial Hospital
      • South Bend, Indiana, United States, 46601
        • Memorial Hospital of South Bend
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Ascension Via Christi Hospitals Wichita
    • Kentucky
      • Owensboro, Kentucky, United States, 42303
        • Owensboro Health Mitchell Memorial Cancer Center
    • Maine
      • Bath, Maine, United States, 04530
        • MaineHealth Coastal Cancer Treatment Center
      • Biddeford, Maine, United States, 04005
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Portland, Maine, United States, 04102
        • Maine Medical Center-Bramhall Campus
      • Sanford, Maine, United States, 04073
        • MaineHealth Cancer Care Center of York County
      • Sanford, Maine, United States, 04073
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
      • Scarborough, Maine, United States, 04074
        • Maine Medical Center- Scarborough Campus
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
      • Columbia, Maryland, United States, 21044
        • Central Maryland Radiation Oncology in Howard County
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital and Medical Center
      • Lowell, Massachusetts, United States, 01854
        • Lowell General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Brownstown, Michigan, United States, 48183
        • Henry Ford Cancer Institute-Downriver
      • Clarkston, Michigan, United States, 48346
        • Michigan Healthcare Professionals Clarkston
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb Hospital-Clinton Township
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Farmington Hills, Michigan, United States, 48334
        • Michigan Healthcare Professionals Farmington
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Pontiac, Michigan, United States, 48341
        • Saint Joseph Mercy Oakland
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital-Royal Oak
      • 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
      • Duluth, Minnesota, United States, 55805
        • Saint Luke's Hospital of Duluth
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Saint Louis, Missouri, United States, 63128
        • Mercy Hospital South
    • Montana
      • Great Falls, Montana, United States, 59405
        • Benefis Healthcare- Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Kalispell Regional Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Dover, New Hampshire, United States, 03820
        • Wentworth-Douglass Hospital
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Mount Holly, New Jersey, United States, 08060
        • Virtua Memorial
      • Toms River, New Jersey, United States, 08755
        • Community Medical Center
      • Voorhees, New Jersey, United States, 08043
        • Virtua Voorhees
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
      • Albuquerque, New Mexico, United States, 87102
        • Lovelace Medical Center-Saint Joseph Square
      • Albuquerque, New Mexico, United States, 87109
        • Lovelace Radiation Oncology
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Oncology Hematology Consultants
      • Santa Fe, New Mexico, United States, 87505
        • Christus Saint Vincent Regional Cancer Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • Rochester, New York, United States, 14642
        • University of Rochester
      • White Plains, New York, United States, 10601
        • Dickstein Cancer Treatment Center
    • North Carolina
      • Cary, North Carolina, United States, 27518
        • Rex Hematology Oncology Associates-Cary
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Garner, North Carolina, United States, 27529
        • Rex Hematology Oncology Associates-Garner
      • Raleigh, North Carolina, United States, 27607
        • UNC Rex Healthcare
      • Raleigh, North Carolina, United States, 27614
        • UNC Rex Cancer Center of Wakefield
      • Raleigh, North Carolina, United States, 27607
        • Rex Hematology Oncology Associates-Blue Ridge
      • Supply, North Carolina, United States, 28462
        • Novant Cancer Institute Radiation Oncology - Supply
      • Wilmington, North Carolina, United States, 28401
        • Novant Health New Hanover Regional Medical Center
      • Wilmington, North Carolina, United States, 28401
        • Novant Health Cancer Institute Radiation Oncology - Wilmington
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
    • Ohio
      • Akron, Ohio, United States, 44307
        • Cleveland Clinic Akron General
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Sylvania, Ohio, United States, 43560
        • ProMedica Flower Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
    • Pennsylvania
      • Harrisburg, Pennsylvania, United States, 17109
        • UPMC Pinnacle Cancer Center/Community Osteopathic Campus
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC-Shadyside Hospital
      • Sayre, Pennsylvania, United States, 18840
        • Guthrie Medical Group PC-Robert Packer Hospital
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
    • South Carolina
      • Greenwood, South Carolina, United States, 29646
        • Self Regional Healthcare
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
    • Texas
      • Austin, Texas, United States, 78705
        • Texas Oncology-Austin Midtown
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
    • Utah
      • Ogden, Utah, United States, 84405
        • Ogden Regional Medical Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Richmond, Virginia, United States, 23226
        • Bon Secours Saint Mary's Hospital
    • Washington
      • Vancouver, Washington, United States, 98686
        • Legacy Salmon Creek Hospital
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • Edwards Comprehensive Cancer Center
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Green Bay, Wisconsin, United States, 54303
        • Saint Vincent Hospital Cancer Center at Saint Mary's
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • West Bend, Wisconsin, United States, 53095
        • Froedtert West Bend Hospital/Kraemer Cancer Center
      • Weston, Wisconsin, United States, 54476
        • Diagnostic and Treatment Center

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:

  • A patient cannot be considered eligible for this study unless all of the following conditions are met.
  • Pathologically confirmed metastatic breast cancer

  • Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis;

    • Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification

  • Number of allowable metastases:

    • =< 4 metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:

      • Peripheral lung
      • Osseous (bone)
      • Spine
      • Central lung
      • Abdominal-pelvic metastases (lymph node/adrenal gland)
      • Liver
      • Mediastinal/cervical lymph node

  • All known disease amenable to metastasis-directed therapy with either SBRT or resection

    • Note: Symptomatic bone metastasis are allowed if ablative therapy can be delivered
    • Note: Sites for possible surgical excision include lung, liver, adrenal gland, bone, small intestine, large intestine, ovary, and amenable nodal disease sites
    • Note: Surgical stabilization is allowed for a metastasis if it is followed by conventionally fractionated external beam radiotherapy
  • Maximum diameter of individual metastasis in any dimension =< 5 cm
  • There are no restrictions on distance between the metastases
  • Patients must be registered within 365 days of the initial metastatic breast cancer diagnosis; first-line standard systemic therapy (chemotherapy, anti-endocrine therapy, anti-HER2, or other standard targeted therapy) for metastatic breast cancer must be given or planned to be given; if given before study entry, it cannot have exceeded a duration of 12 months at the time of registration (Note: sequencing of ablative therapy [surgery or SBRT] relative to systemic therapy, for patients randomized to Arm 2, is at the discretion of the treating physician)

  • The primary tumor site must be controlled prior to registration

    • For those who present with synchronous primary and oligometastatic disease, primary must be controlled prior to registration
    • The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference For those who present with local recurrence and oligometastatic disease, local recurrence must be controlled prior to registration
    • The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference

  • Appropriate stage for study entry based on the following diagnostic workup:

    • History/physical examination within 60 days prior to registration
    • Clinical grade computed tomography (CT) scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT within 60 days prior to study registration
  • Zubrod performance status =< 2 within 60 days prior to registration
  • Blood cell count (CBC)/differential obtained within 60 days prior to registration on study
  • Absolute neutrophil count (ANC) >= 500 cells/mm^3
  • Platelets >= 50,000 cells/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)
  • For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

  • Patients with any of the following conditions are NOT eligible for this study.
  • Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;
  • Co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years; previous RT dose, date, fraction size, must be reported

  • Metastases with indistinct borders making targeting not feasible

    • Note: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician's judgment will be required
  • Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)

  • 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)
    • Brainstem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
    • Whole lung previously irradiated with prior percent volume receiving greater than or equal to 20 Gy (V20Gy)> 30% (delivered in =< 3 Gy/fraction)
    • Primary tumor irradiated with SBRT
    • Metastasis irradiated with SBRT
  • Brain metastases
  • Exudative, bloody, or cytological proven malignant effusions

  • Severe, active co-morbidity defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • 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 at the time of registration
  • Pregnancy; lactating females must cease expression of milk prior to signing consent to be eligible
  • 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 cluster of differentiation 4 (CD4) count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol

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
No Intervention: Standard of Care (SOC)
Standard of care systemic therapy at the discretion of the treating physician.
Experimental: Standard of Care + Ablation
Standard of care systemic therapy plus ablation of all metastases by stereotactic body radiotherapy or surgery at the discretion of the treating physician.
Radiation: Stereotactic Body Radiotherapy

Patients receive 1, 3, or 5 fractions of radiation, beginning within 6 weeks of study entry.

  • For metastases in the peripheral lung, patients receive a single fraction of 30 Gy or 3 fractions for a total of 45 Gy.
  • For a single liver metastases, patients receive a single fraction of 30 Gy.
  • For metastases in the abdominal-pelvic or liver (>1), patients receive 3 fractions for a total of 45 Gy.
  • For metastases in the central lung or mediastinal/ cervical lymph nodes, patients receive 5 fractions for a total of 50 Gy.
  • For spinal metastases, patients receive 1 fraction of 20 Gy.
  • For non-spinal osseous metastases, patients receive 3 fractions for a total of 30 Gy.
  • For thoracic/cervical spine metastases, patients receive 5 fractions for a total of 35 Gy.
Other Names:
  • SBRT
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • Stereotactic Radiosurgery
  • stereotactic ablative radiotherapy (SABR)
Procedure: Surgery
All surgical resections will be approached with intent of an R0 resection (rendering the patient with no evidence of measureable disease and pathologic negative margin) and must occur within 6 weeks of study entry. Approach to surgery will be based upon the treating surgeon. An open, laparoscopic, or thorascopic approach is acceptable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (Phase II)
Time Frame: From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months, then every six months to five years, then annually. Maximum follow-up at time of analysis was 63 months.
Progression (failure) is defined as any of the following: progression of metastases, new metastases, or death. Progression-free survival (PFS) time is defined as time from randomization to the date of first progression, death, or last contact when participant had a documented clinical assessment (censored). PFS rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Median PFS is provided.
From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months, then every six months to five years, then annually. Maximum follow-up at time of analysis was 63 months.
Overall Survival (Phase III)
Time Frame: From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months and then annually. Maximum follow-up at time of analysis was 63 months.
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored).
From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months and then annually. Maximum follow-up at time of analysis was 63 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Treated Metastasis Progression on the SOC + Ablation Arm
Time Frame: From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months. Two-year rates are provide here.
Metastasis progression (failure) is defined as the clearance and subsequent recurrence or the development of new metastases in the treated area. Failure time is defined as time from randomization to the date of first failure, last contact when participant had a documented clinical assessment (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method. Two-year failure rates are provided here.
From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months. Two-year rates are provide here.
Percentage of Participants With New Metastases
Time Frame: From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.
New metastases (failure) is defined as the appearance of any new metastases. Failure time is measured from randomization to the date of first failure, last contact when participant had a documented clinical assessment (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year failure rates are provided here
From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.
Number of Patients by Highest Grade Adverse Event Reported
Time Frame: From randomization to last follow-up. Follow-up schedule: Arm 1: 3 mos. after randomization / Arm 2: weekly during SBRT and the last day of SBRT; both arms: then every 3 mos. to 24 mos., then annually. Maximum follow-up at time of analysis was 63 months.
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
From randomization to last follow-up. Follow-up schedule: Arm 1: 3 mos. after randomization / Arm 2: weekly during SBRT and the last day of SBRT; both arms: then every 3 mos. to 24 mos., then annually. Maximum follow-up at time of analysis was 63 months.
Progression-free Survival in the Presence or Absence of Circulating Tumor Cells (CTCs)
Time Frame: From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.
The presence of CTCs is defined as ≥ 5 CTCs (per 7.5ml of blood). Progression (failure) is defined as any of the following: progression of metastases, new metastases, or death. Progression-free survival (PFS) time is defined as time from randomization to the date of first progression, death, or last contact when participant had a documented clinical assessment (censored). PFS rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the groups, which is reported in the statistical analysis results. Two-year PFS rates are provided here
From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.

Collaborators and Investigators

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

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Steven J Chmura, NRG Oncology

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.

General Publications

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)

December 24, 2014

Primary Completion (Actual)

December 20, 2021

Study Completion (Estimated)

December 20, 2026

Study Registration Dates

First Submitted

February 5, 2015

First Submitted That Met QC Criteria

February 10, 2015

First Posted (Estimated)

February 18, 2015

Study Record Updates

Last Update Posted (Actual)

January 11, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-BR002 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2014-01810 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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