Clinical Trials Logo

Clinical Trial Summary

The purpose of this study is to evaluate feasibility to treat metachronous multi-site breast cancer oligometastasis with stereotactic body radiotherapy (SBRT) in patients on systemic therapy.

Clinical Trial Description

Patients who present with or develop metastatic breast cancer after initial therapy are typically considered incurable. Treatments offered are to relieve symptoms and are palliative in intent, including chemotherapy, hormonal therapy, biologics (e.g. trastuzumab for Her2 positive disease), bisphosphonates (for bone protection), palliative radiotherapy for symptom relief, and supportive care. Prognosis is guarded, with median OS estimated at 2-3 years, and progression free survival (PFS) approximately 9-12 months.

Based on research observing the natural history of breast cancer, it was discovered that some cancers have a predilection for spread to a limited number of sites and remain in these sites for a number of months before acquiring widespread malignant potential. This is defined as the oligometastatic state, and patients with up to five sites of disease are said to have oligometastatic (OM) cancer. A number of studies of systemic therapy in metastatic breast cancer have reported that patients with OM disease have a better prognosis compared to other patients with more widespread disease, and in particular in patients with bone-only metastastic breast cancer, outcomes may be better.

In the setting of OM disease in particular, local therapies could be considered. For example, metastatectomies have been adopted into clinical practice in patients with colorectal cancer liver metastases and sarcoma lung metastases with encouraging long-term outcomes. In the case of metastatic breast cancer, there is less data to support a local therapy approach. Breast cancer patients in particular commonly present with metastatic bone, lung and liver disease. Some of these sites, for example bony or spinal disease, are not as easily amenable to surgical resection, and surgery itself can cause significant morbidity. In such patients, it would be desirable to consider a locally ablative therapy that is non-invasive, versatile (can treat multiple sites simultaneously); generalizable to patients of various performance statuses; have low rates of toxicity; and be proven to eradicate disease in treated areas.

Standard conformal radiotherapy (RT) is traditionally used for the treatment of metastatic breast cancer. The main indication for RT has been with palliative intent, and relatively low doses are used with the goal of symptom control. Higher RT doses given in 5-6 weeks (50-60 Gy/25-30 fractions) may improve local control (LC); however they are inconvenient and may be associated with increased acute toxicity. Over the past 10 years, due to technical advances in RT planning and delivery, the ability to precisely and safely deliver larger daily doses over shorter periods of time has developed, known as stereotactic body radiotherapy (SBRT). This technique is defined by the Canadian Association of Radiation Oncology as: "The precise delivery of highly conformal and image-guided hypo-fractionated external beam radiotherapy, delivered in a single or few fraction(s), to an extra-cranial body target with doses at least biologically equivalent to a radical course when given over a conventionally fractionated (1.8-3.0 Gy/fraction) schedule". SBRT is a non-invasive method involving delivery of multiple small radiation beams from many angles with sub-millimetre precision, targeted to eradicate intracranial lesions. The goal is to use large ablative doses to achieve permanent tumour control with 1-6 fractions of 5-20 Gy per fraction. Ultimately this represents a philosophical shift in treating a metastatic site with locally "ablative" doses of radiation in a safe, effective, and convenient fashion.

There is growing evidence to support the safety and efficacy of SBRT to many single organ sites, and literature reviews demonstrate LC of 70-90% in OM sites at 1-2 years. A recent systematic review of the literature of ablative therapies in metastatic breast cancer (including SBRT) revealed significant heterogeneity in observed studies, and no clearly definable subgroups that may benefit, with the exception of patients who had complete ablation of their residual disease. The conclusion from this study was that further clinical trials were necessary to demonstrate benefit of ablative therapies as compared to standard treatment in breast OM.

Therefore, while SBRT has been used safely and effectively to treat OM evidence suggests there is still a need in better characterizing the role of SBRT with respect to local control, freedom from distant progression and potentially survival. The investigators believe that patients with metastatic breast cancer are likely to benefit from SBRT for a number of reasons: 1) a significant portion of patients develop OM disease; 2) the most common breast OM sites including bone, liver and lung are amenable to SBRT; 3) with improvements in systemic therapy, there is a high probability that microscopic (non-clinically evident) metastatic disease will be controlled, so that additional local therapy may be synergistic and improve local control and symptom development in the future. Notwithstanding these factors, SBRT to bony and other sites is rarely used in metastatic breast cancer patients in Canada for several reasons: there is a gap in knowledge regarding the potential role of SBRT in these patients, a current pattern of referrals and triage for more traditional palliative treatments, and lack of standardized protocols to treat, assess response and follow these patients. The investigators propose a feasibility study, which addresses these issues in patients with OM breast cancer to bony and visceral sites, which may provide the background foundation for future research and patient care. The study aims to address not only feasibility, but local control, survival, toxicity, and quality of life. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT03295916
Study type Interventional
Source Juravinski Cancer Center
Contact Elysia Donovan, MD,FRCPC
Phone 9053879495
Status Not yet recruiting
Phase Early Phase 1
Start date October 1, 2017
Completion date April 1, 2020

See also
  Status Clinical Trial Phase
Recruiting NCT03095352 - A Randomized Phase II Study of Pembrolizumab, an Anti-PD (Programmed Cell Death)-1 Antibody, in Combination With Carboplatin Compared to Carboplatin Alone in Breast Cancer Patients With Chest Wall Disease Phase 2
Active, not recruiting NCT01472094 - Clinical and Biological Predictors of Chemotherapy Toxicity in Older Adults
Recruiting NCT03544762 - Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation Phase 3
Recruiting NCT03284957 - Phase 1 / 2 Study of SAR439859 Single Agent and in Combination With Palbociclib in Postmenopausal Women With Estrogen Receptor Positive Advanced Breast Cancer Phase 1/Phase 2
Completed NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Active, not recruiting NCT01857193 - Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer Phase 1
Recruiting NCT03432429 - REI-EXCISE iKnife Study N/A
Active, not recruiting NCT02139358 - Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer Phase 1/Phase 2
Completed NCT03323333 - Psychosocial Intervention Pilot for Partners in BRCA Testing N/A
Terminated NCT01649258 - Fosaprepitant Dimeglumine and Granisetron Transdermal System in Preventing Nausea and Vomiting in Patients With Breast Cancer Undergoing Chemotherapy Phase 1
Completed NCT03384511 - The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies. Phase 4
Recruiting NCT01992432 - Brain Functional MRI in Older Women With Breast Cancer (Brain fMRI-BC)
Completed NCT01943500 - Collection of Blood Specimens for Circulating Tumor Cell Analysis N/A
Not yet recruiting NCT03433313 - Efficacy and Safety Study of EG12014 Compared With Herceptin in Subjects With HER2 Positive Early Breast Cancer Phase 3
Completed NCT02371174 - Post-Marketing Surveillance Study of Eribulin on the Status and Factors for the Development of Peripheral Neuropathy in Japan.
Not yet recruiting NCT03273348 - Role of Oncoplastic Breast Surgery In Breast Cancer Treatement N/A
Active, not recruiting NCT02225470 - Eribulin Versus Vinorelbine in Subjects With Locally Recurrent or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes Phase 3
Completed NCT01881230 - Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer) Phase 2/Phase 3
Recruiting NCT03324932 - Efficacy of Denosumab on Normal BMD in Women Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer Phase 3
Recruiting NCT03237572 - Focused Ultrasound and Pembrolizumab in Metastatic Breast Cancer Phase 1