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.

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

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
Phase II/III
Benjamin Bridges , M.D.
NRG (NRG Oncology)

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.