The investigators propose to treat patients with metastatic esophageal cancers and dysphagia with two fractions of brachytherapy followed by pembrolizumab. The brachytherapy is hypofractionated and will provide a radiation dose of sufficient intensity to induce the release of tumor-derived antigens and trigger an antitumor immune response. The simplicity of the design should maximize the chance to examine the hypothesis that radiotherapy can induce an immune response, which can then be augmented by pembrolizumab treatment. Success in this study would provide the impetus to conduct further trials aimed at developing this unique strategy as a more broadly applicable therapeutic option in the treatment of patients suffering from these deadly cancers, and will provide important mechanistic insights into the relationship between radiation treatment and immune therapy augmentation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Provided by Merck.
It will be delivered using a high-dose-rate Ir-192 afterloader via a dedicated esophageal applicator.
Washington University School of Medicine
St Louis, Missouri, United States
Safety as Measured by Number of Participants With Grade 3 or Higher Treatment Related Adverse Events
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 will be utilized for all toxicity reporting. In general, CTCAE version 4.03 has the following definitions for the grading scale: Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time frame: Through 30 days after completion of treatment (median length of adverse event follow-up 106 days, full range 42-1023 days)
Mean Percent Change in Esophageal Tumor Length as Measured by Endoscopy
Time frame: Prior to brachytherapy and once anytime between 2-6 months after start of pembrolizumab (up to approximately 7 months post-baseline)
Change in Esophageal Lumen Size as Measured by Endoscopy
Time frame: Prior to brachytherapy, at 1-2 weeks after initiation of brachytherapy (optional), and 2-6 months after start of pembrolizumab
Worst Grade of Dysphagia Experienced by Participant
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 will be utilized for all toxicity reporting. Grade 1: symptomatic, able to eat regular diet; Grade 2: symptomatic and altered eating/swallowing; Grade 3: severely altered eating/swallowing; tube feeding or TPN or hospitalization indicated; Grade 4: life-threatening consequences; urgent intervention indicated; Grade 5: death.
Time frame: From start of treatment through 8 weeks post-pembrolizumab (median length of dysphagia follow-up 132 days, full range 42-1049 days)
Overall Response as Measured by Immune-Related Response Criteria (irRC)
\- Response and progression will be evaluated in this study using Immune-Related Response Criteria. * irCR, complete disappearance of all lesions (whether measurable or not, and no new lesions) - confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented * irPR, decrease in tumor burden ≥ 50% relative to baseline - confirmed by a consecutive assessment at least 4 weeks after first documentation * irSD, not meeting criteria for irCR or irPR, in absence of irPD * irPD, increase in tumor burden ≥ 25% relative to nadir (minimum recorded tumor burden) - confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented * Patients are considered to have irPR or irSD even if new lesions are present as long as they meet the respective thresholds of response as described above. Furthermore, patients are not considered to have irPD if new lesions are present and the tumor burden of all lesions.
Time frame: Through completion of treatment (median length of treatment 76 days, full range 25-993 days)
Median Progression-free Survival (PFS)
PFS was defined as the duration from the first infusion of pembrolizumab until disease progression or death (whichever occurred first).
Time frame: Up to 1 year after completion of treatment (median length of treatment 76 days, full range 25-993 days)
Median Overall Survival (OS)
OS was defined as the duration from the first infusion of pembrolizumab until death.
Time frame: Up to 1 year after completion of treatment (median length of treatment 76 days, full range 25-993 days)
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