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NRG-BR002: 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

Description

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 (SBRT), 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.

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of this clinical trial is progression-free survival.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have pathologically confirmed metastatic breast cancer
  • Have known estrogen, progesterone, and HER2 status of either primary tumor or metastasis
  • Have less than four metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:
    • Peripheral lung
    • Bone
    • Spine
    • Central lung
    • Abdominal-pelvic (lymph node/adrenal gland)
    • Liver
    • Mediastinal/cervical lymph node
  • Have 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.
  • Have a maximum diameter of individual metastasis in any dimension less than 5 cm (There are no restrictions on distance between the metastases.)
  • Are registered within 365 days of the initial metastatic breast cancer diagnosis (First-line standard systemic therapy, such as 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. Sequencing of ablative therapy, such as surgery or SBRT, relative to systemic therapy, for patients randomized to Arm 2, is at the discretion of the treating physician.)
  • Agree 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.
  • Have appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 60 days prior to registration
    • Clinical grade computed tomography scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body positron emission tomography within 60 days prior to study registration
    • Zubrod performance status less than two within 60 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

Excluding patients who:

  • Have pathologic evidence of local/regional breast tumor recurrence at the time of registration
  • Have co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of three years; previous RT dose, date, fraction size, must be reported
  • Have 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.)
  • Had prior palliative radiation treatment for metastatic disease (including radiopharmaceuticals)
  • Have 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 V20Gy > 30% (delivered in ≤ 3 Gy/fraction)
  • Had primary tumor irradiated with SBRT
  • Had metastasis irradiated with SBRT
  • Have brain metastases
  • Have exudative, bloody, or cytological proven malignant effusions
  • Have 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 less than 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 greater than or equal to 200 cells/microliter within 30 days prior to registration (Note also that HIV testing is not required for eligibility for this protocol.)