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

Status
Temporarily Closed
Cancer Type
Bone Tumor
Breast Cancer
Trial Phase
Phase II
Phase III
Eligibility
18 Years and older, Female
Study Type
Treatment
NCT ID
NCT02364557
Protocol IDs
NRG-BR002 (primary)
NCI-2014-01810
Study Sponsor
NRG Oncology

Summary

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.

Objectives

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

SECONDARY OBJECTIVES:
I. To evaluate treated metastasis control according to tumor receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor [HER]-2), 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).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM 1: Patients continue to receive their current planned systemic therapy at the discretion of the treating physician.

ARM 2: 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.

ARM 1: Patients are followed every 3 months from randomization to 2 years.
ARM 2: Patients are followed 25-35 days post-ablation, every 3 months from randomization to 2 years, and then yearly thereafter.

Eligibility

  1. A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
  2. Pathologically confirmed metastatic breast cancer
  3. Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis; * Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
  4. 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
  5. 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
  6. Maximum diameter of individual metastasis in any dimension =< 5 cm
  7. There are no restrictions on distance between the metastases
  8. 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)
  9. 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
  10. 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
  11. Zubrod performance status =< 2 within 60 days prior to registration
  12. Blood cell count (CBC)/differential obtained within 60 days prior to registration on study
  13. Absolute neutrophil count (ANC) >= 500 cells/mm^3
  14. Platelets >= 50,000 cells/mm^3
  15. Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  16. For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration
  17. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Treatment Sites in Georgia

Emory University Hospital - Midtown


550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

Piedmont Hospital - Atlanta


1968 Peachtree Road, NW
Atlanta, GA 30309
www.piedmont.org

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
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Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.