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Standard of Care Therapy With or Without Stereotactic Radiosurgery and/or Surgery in Treating Patients With Limited Metastatic Breast Cancer

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2016 by NRG Oncology
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology
ClinicalTrials.gov Identifier:
NCT02364557
First received: February 5, 2015
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Dyspnea Fatigue Nausea and Vomiting Pain Stage IV Breast Cancer Radiation: Stereotactic Radiosurgery Procedure: Therapeutic Conventional Surgery Other: Laboratory Biomarker Analysis Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by NRG Oncology:

Primary Outcome Measures:
  • Progression-free survival (failure: progression or death due to any cause) (Phase II-R) [ Time Frame: From the date of randomization to the date of first PFS failure or last follow-up; assessed up to 3 years ]
    Progression-free survival will be estimated by the Kaplan-Meier method, with progression defined as: progression of initial/treated metastases (using the revised Response Evaluation Criteria in Solid Tumors [RECIST] guideline), appearance of new metastases, or death due to any cause. The distribution of PFS estimates between the two arms will be compared using the log rank test.

  • Overall survival (failure: death due to any cause) (Phase III) [ Time Frame: From the date of randomization to the date of death or last follow-up; assessed up to 8 years ]
    Overall survival will be estimated by the Kaplan-Meier method. The distribution of OS estimates between the two arms will be compared using the log rank test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with OS.


Secondary Outcome Measures:
  • Appearance of new metastases [ Time Frame: From the date of randomization to the date of the first appearance of any new metastases; assessed up to 8 years ]
    Failure for this endpoint will be the appearance of any new metastases. The cumulative probability of new metastases in the presence of competing failure events will be estimated by the cumulative incidence method. The cumulative incidence distributions between the two arms will be compared using Gray's test. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with the incidence of new metastases.

  • Incidence of adverse events graded according to National Cancer Institute CTCAE version 4 [ Time Frame: From the date of randomization to the date of death or last follow-up; assessed up to 2 years ]
    The frequencies and severity of adverse events by treatment arm will be analyzed.

  • Initial presence of CTCs in blood samples [ Time Frame: Baseline ]
    The prognostic effect of the initial presence of CTCs at baseline on PFS (OS) will be evaluated using the Cox proportional hazards model, controlling for treatment effect and stratification factors. The hypothesis tests will be two-sided and will use an alpha level of 0.05 to determine significance.

  • Presence of CTCs after treatment in blood samples [ Time Frame: Up to 3 months ]
    The interaction between treatment effect and the initial presence of CTCs at baseline on PFS (OS) will be evaluated in the Cox model, which will include an indicator for treatment group, an indicator for presence of CTCs (>= 5 per 7.5 ml of blood), and their interaction term. The analysis will be adjusted for the stratification factors.

  • Change in CTC count in blood samples [ Time Frame: Baseline to up to 3 months ]
    The effect of change in CTC count from CTC >= 2 per 7.5 ml of blood at baseline to CTC = 0 at follow-up after initial treatment on PFS (OS) will be evaluated using the Cox proportional hazards model, controlling for treatment effect and stratification factors. The analyses will be conditional on a patient's event-free survival up to post-treatment evaluation. The interaction between treatment effect and change in CTC count will be evaluated in the Cox model, which will include an indicator for treatment group, an indicator for change of CTCs, and their interaction term.

  • Levels of ctDNA in plasma samples [ Time Frame: Up to 3 months ]
    The prognostic effect of dichotomized ctDNA on PFS (OS) will be evaluated using the Cox proportional hazards model, controlling for treatment effect and stratification factors. In addition, the presence of the interaction between treatment effect and dichotomized ctDNA will be evaluated (predictive effect). Spearman rank correlation coefficient will be used to correlate the levels of CTCs and ctDNA.


Estimated Enrollment: 402
Study Start Date: December 2014
Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Arm 1 (standard of care)
Patients continue to receive their current planned systemic therapy at the discretion of the treating physician.
Experimental: Arm 2 (stereotactic radiosurgery, surgery)
Patients continue to receive their current planned systemic therapy at the discretion of the treating physician. Patients also undergo stereotactic radiosurgery in 1, 3, or 5 fractions within 3 weeks and/or surgery at the discretion of the treating physician.
Radiation: Stereotactic Radiosurgery
Undergo stereotactic radiosurgery
Other Names:
  • SBRT
  • Stereotactic External Beam Irradiation
  • Stereotactic Radiation Therapy
  • Stereotactic Radiotherapy
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Other: Laboratory Biomarker Analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed metastatic breast cancer within 270 days prior to registration
  • Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis
  • =< 2 metastases seen on standard imaging within 30 days prior to registration
  • Controlled primary tumor site defined as >= 3 months (90 days) recurrence-free interval since completion of definitive surgical management
  • 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
  • Metastases must be > 5 cm away from each other (defined as Edge to Edge of tumor)

    • NOTE: If metastases are =< 5 cm away from each other, consider enrollment in NRG-BR001
  • First-line standard systemic therapy (chemotherapy, anti-endocrine therapy, anti-HER2 or other standard targeted therapy) for metastatic breast cancer not to have exceeded a duration of 6 months at the time of registration
  • Appropriate stage for study entry based on the following diagnostic workup:

    • History/physical examination within 30 days prior to registration
    • Computed tomography (CT) scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT within 30 days prior to study registration
  • Zubrod performance status =< 2 within 30 days prior to registration
  • 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 must provide study-specific informed consent prior to study entry

Exclusion Criteria:

  • Pathologic evidence of local/regional breast tumor recurrence
  • Co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years
  • 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
  • Metastases located within 3 cm of the previously irradiated structures:

    • Spinal cord previously irradiated to > 40 Gy
    • Brachial plexus previously irradiated to > 50 Gy
    • Small intestine, large intestine, or stomach previously irradiated to > 45 Gy
    • Brainstem previously irradiated to > 50 Gy
    • Lung previously irradiated with prior V20Gy > 30%
  • 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 CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02364557

  Show 53 Study Locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven Chmura NRG Oncology
  More Information

Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT02364557     History of Changes
Other Study ID Numbers: NRG-BR002
NCI-2014-01810 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-BR002 ( Other Identifier: NRG Oncology )
NRG-BR002 ( Other Identifier: CTEP )
U10CA180868 ( US NIH Grant/Contract Award Number )
Study First Received: February 5, 2015
Last Updated: June 17, 2016

Additional relevant MeSH terms:
Breast Neoplasms
Fatigue
Vomiting
Dyspnea
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Signs and Symptoms, Digestive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory

ClinicalTrials.gov processed this record on June 23, 2017