Abstract OT3-03-04: NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer
Authors: Chmura SJ , Winter KA , Salama JK , Woodward WA , Borges VF , Al-Hallaq H , Matuszak M , Jaskowiak NT , Milano MT , Bandos H , White JR 
Published: May 2016

Abstract
Background:
The current standard of care for metastatic breast cancer patients (pts) is to deliver palliative chemotherapy, biologic &/or hormonal therapy when appropriate, with radiation &/or surgery reserved for the management of symptomatic or non-responsive (mets). For selected pts with limited metastatic (met) disease, mets-directed ablative therapy, with either surgical resection or high dose conformal radiotherapy (in addition to standard systemic therapies) to lung, liver, CNS adrenal, & multiple organs has been shown to result in long-term disease control numerically superior to systemic therapy alone. NRG-BR002 is a randomized Phase II trial to evaluate stereotactic body radiotherapy (SBRT) &/or surgical resection (SR) of all met sites in newly oligometastatic breast cancer in addition to standard systemic therapy.
Trial Design & Eligibility
For the Ph IIR, eligible breast cancer pts who have received up to 6 months of first line systemic therapy without progression will be randomized to receive either standard systemic therapy with mets directed therapy as needed ( control arm) versus ablative therapy of all met sites with either body SBRT &/or surgical resection (SR) ( per the treating physician discretion) to determine if there is an improvement median progression free survival (PFS). If this aim is met the trial continues as a Ph III to evaluate if SBRT/SR improves 5 year overall survival. Secondary aims include local control in the met site, new distant met rate, & technical quality. The primary translational endpoint tests whether &lt; 5 CTCs (per 7.5ml of blood) is an independent prognostic (outcome) marker for improved PFS & OS in oligometastatic breast cancer.
Women with pathologically confirmed met breast cancer to &lt; /= 2 sites, with up to 6 months of standard first line systemic therapy & the primary site disease is controlled. CNS mets are ineligible. ER/PR & HER-2 neu are required on either the primary or met site. Site radiation credentialing & a facility questionnaire are required. Randomization is to standard systemic therapy with local radiotherapy/ surgery for palliation when necessary vs ablative therapy of all mets with SBRT &/or SR.
Statistics:
For the Ph IIR portion to detect a signal for improved median PFS from 10.5 months to 19 months with 95% power & accounting for ineligible/lost pts, 146 pts will be required. For the Ph III, an additional 246, for a total of 402 pts will be required to definitively determine if ablative therapy improves 5-year overall survival from 28% to 42.5% (HR=0.67), with 85% power & a 1-sided type I error of 0.025. For the translational research, the number of pts accrued in the Ph IIR & Ph III portions will provide sufficient power ≥ 91% to detect whether &lt; 5 CTC's is a prognostic marker for improved PFS & OS.
Present Accrual & Target Accrual
NRG BR002 activated 12/24/2014 with a target accrual of 146 pts for the Ph II component & 256 additional for the Ph III.
Contact Information:
Protocol: CTSU member web site https://www.ctsu.org. Enrollment: OPEN at https://open.ctsu.org.
Support:
Supported by NRG Oncology grants U10CA180868 & U10CA180822 from the National Cancer Institute (NCI).
Citation Format: Chmura SJ, Winter KA, Salama JK, Woodward WA, Borges VF, Al-Hallaq H, Matuszak M, Jaskowiak NT, Milano MT, Bandos H, White JR. NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-03-04.