Clinical trial NCT03295916: Stereotactic Body Radiotherapy for Patients With Breast Cancer Oligometastasis
Official title: Stereotactic Body Radiotherapy (SBRT) for the Treatment of OligoMetastasis in Breast Cancer Patients (STOMP): A Prospective Feasibility Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Breast Cancer
Lead sponsor: Juravinski Cancer Center
Sponsor class: OTHER
Collaborators: name: Toronto Sunnybrook Regional Cancer Centre
First posted: 2017-09-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of newly metastatic breast cancer with a disease-free interval of at least six months from initial completion of primary breast cancer (stage I-III) treatment (including net-adjuvant or adjuvant chemotherapy, but excluding hormonal or targeted therapies).

   Adequate definitive primary treatment is required, including partial or complete mastectomy, standard partial breast, whole breast or loco-regional radiotherapy, with or without hormonal therapy or chemotherapy. Note patients must be offered systemic therapy prior to radiotherapy, if deemed fit for treatment. Systemic therapy (including chemotherapy, hormonal therapy, or targeted therapy may have been initiated within the previous 12 months, or commence following SBRT. Alternatively patients may develop breast OM while on any adjuvant hormonal therapy provided at least six months have passed since definitive local treatment or chemotherapy;
2. No more than 12 months may have passed since diagnosis of OM disease;
3. Total burden of disease limited to 5 metastatic sites or less, and the size of each metastatic lesion must be less than 5 centimeters;
4. All lesions amenable to SBRT (lesions may overlap if treatable at discretion of Radiation Oncologist).

Exclusion Criteria:

1. Previous radiotherapy to same site or vicinity preventing definitive SBRT (eg. within 5 cm);
2. Unacceptable fracture risk according to clinician judgement for bone lesions;
3. Brain metastasis, spinal cord compression, superior vena cava obstruction;
4. Bone lesions inside the femoral head/neck;
5. Patients refusing or deemed ineligible for systemic (chemotherapy, hormonal therapy or targeted therapy);
6. History of major radiosensitivity syndrome or contraindications to radiotherapy;
7. Second invasive malignancy within the past 3 years (excluding non-melanomatous skin cancer);
8. Inability to lie supine for 60 minutes of treatment;
9. Currently pregnant or lactating;
10. Psychiatric or addictive disorders precluding informed consent or adherence to protocol;
11. Geographic inaccessibility for follow-up;
12. Performance status Eastern Cooperative Oncology Group 3 or worse;
13. Inadequate organ function: complete blood count, liver function tests including albumin, bilirubin and International nominalized ratio (INR) (for liver SBRT);
14. Less than 18 years of age.

Primary outcomes:
measure: Technical feasibility of planning SBRT to multiple sites
timeFrame: Two weeks from consent
Secondary outcomes:
measure: Toxicity: Incidence of treatment-emergent adverse events [safety and tolerability] as assessed by CTCAE 4.0
timeFrame: One week, 3,6, 12 months from SBRT treatment
measure: Feasibility of patient accrual: Successful accrual of 30 patients to study
timeFrame: At 12 months from study initiation
measure: Local Control: CT scan or MRI as assessed by RECIST criteria 1.1
timeFrame: 3, 6, 12 months from SBRT treatment
measure: Progression Free Survival (PFS)
timeFrame: 3, 6, 12 months from SBRT treatment
measure: Overall Survival (OS)
timeFrame: 3, 6 12 months from SBRT treatment
measure: Quality of Life defined by EORTC Quality of Life Questionnaire core-30
timeFrame: One week, 3, 6, 12 months from SBRT treatment
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
Study officials:
affiliation: McMaster University
name: Anand Swaminath, MD,FRCPC
role: PRINCIPAL_INVESTIGATOR
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