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
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.
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).
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;
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:
All known disease amenable to metastasis-directed therapy with either SBRT or resection
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
Appropriate stage for study entry based on the following diagnostic workup:
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
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:
Brain metastases
Exudative, bloody, or cytological proven malignant effusions
Severe, active co-morbidity defined as follows:
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
Sacramento, California 95817, United States
Brownstown, Michigan 48183, United States
Lebanon, New Hampshire 03756, United States
New York, New York 10032, United States
Wilmington, North Carolina 28401, United States
Harrisburg, Pennsylvania 17109, United States
Stevens Point, Wisconsin 54482, United States
Montreal, Quebec H3H 2R9, Canada