This is a prospective, observational pilot study that will describe the safety profile and biological effects of combining stereotactic ablative body radiosurgery (SABR) treatment (20Gy/1#) and a PD-1 antibody, MK-3475. 15 patients with oligometastatic breast cancer with at least one lesion considered safe for SABR radiotherapy, will be treated with SABR for their oligometatastic disease in addition to 6 months of MK-3475 treatment (1 cycle every 3 weeks, a total of 8 cycles). This investigator driven pilot study will examine the safety and biological effects of combining MK-3475 (Pembrolizumab) an antibody targeted against the anti-programmed cell death 1 (PD-1) T cell checkpoint, with SABR therapy for oligometastatic disease. We hypothesise that the safety profile of this combination, will be clinically acceptable and well tolerated for patients, and that we will observe evidence of systemic immune activation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Stereotactic Ablative Body Radiosurgery (SABR) - a single 20Gy in 1 fraction.
MK-3475 (200mg IV) on day 1 every 3 weeks for a total of 8 cycles.
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Safety Profile - Summary of acute and long term adverse events as assessed by CTCAE v4.0
Safety profile will be evaluated using CTCAE v4.0 in all patients who have received at least one SABR treatment and one dose of MK-3475. Acute AE are defined as AE's occurring from the time from 1st SABR treatment to 30 days post end of MK-3475 treatment and long term AE are defined as AE's occurring after 30 days post end of MK-3475 treatment.
Time frame: 24 months
Immunological Effects - Changes in immunological markers within tumor tissue, and immune subsets in peripheral blood over serial time-points, including at time of progression.
Blood samples will be collected (50ml) at baseline (prior to first SABR), prior to the first dose of MK-3475, prior to cycle 2 of MK-3475, at disease progression (if this occurs) and then every 3 months up to two years post end of SABR treatment. These will be analysed for the following (this is a non-exhaustive list): i. Absolute lymphocyte counts using a blood analyser. ii. The presence of CD8+ T cells by flow cytometric analysis. iii. Change in frequency of tumor reactive T cells. These may include markers for HLA-DR, CD4+, CD8+ T cells, PD-1, TIM-3 signifying antigen presentation and experience.
Time frame: 24 months
Treatment Effectiveness - Pain Scale. Changes in pain levels as assessed by the Numeric Pain Rating Scale.
Pain levels will be evaluated pre and post-treatment using the Numerical Rating Pain Scale at the following time points: pre-SABR treatment, at approximately 1 month, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and at 24 months after the end of SABR treatment.
Time frame: 24 months
Treatment Efficacy - Local Progression Free Survival (LPFS)
LPFS will be assessed at baseline, 1 month post SABR treatment, then at every three months for 24 months or until the date of first local progression, or date of death for patients without local progression.
Time frame: 24 months
Tumor Efficacy - Distant Progression Free Survival (DPFS)
DPFS will be assessed at baseline, 1 month post SABR treatment, then at every three months for 24 months or until the date of first local progression, or date of death for patients without distant progression.
Time frame: 24 months
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