The purpose of this research is to evaluate whether adding histotripsy to maintenance durvalumab increases immune response and to assess the safety of this combination for participants with advanced intrahepatic cholangiocarcinoma (iCCA). Histotripsy is a non-invasive, non-thermal treatment that uses focused ultrasound energy to destroy tumor tissue. 12 people will be enrolled in this study.
Participant diagnosed with histologically confirmed intrahepatic cholangiocarcinoma
Participant demonstrates disease control following 18 weeks of chemotherapy (gemcitabine and/or cisplatin) and immunotherapy (durvalumab) as part of standard of care first line regimen.
Participants are allowed to be on maintenance durvalumab therapy following disease control at 18 weeks prior to enrollment into the study.
All participants must have prior biopsy confirming diagnosis of cholangiocarcinoma.
Participant is pregnant or planning to become pregnant or nursing (lactating) during the trial period.
Participant is enrolled in another investigational trial and/or is taking investigational medication or treated with an investigational device ≤30-days prior to planned histotripsy procedure date.
In the Investigator's opinion, the subject has co-morbid disease(s) or condition(s) that would cause undue risk and preclude safe histotripsy treatment, including but not limited to interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. .
Single group
Histotripsy
DeviceHistotripsy will be performed using the Edison® System (HistoSonics, Inc.), which is FDA cleared for destruction of liver tissue using non thermal focused ultrasound. Performed on Cycle 1 Day 8 (C1D8) to treat the Target Tumor.
Durvalumab
DrugDurvalumab is an immunotherapy drug and will be administered on day 1 of each 28-day cycle as per local standards. Dosing of maintenance durvalumab is 1500mg IV per FDA labeling with administration performed over 60 minutes as per standard clinical practice.
Biopsy
Procedure/SurgeryTwo research biopsies are planned for cycle 1 day 3 and cycle 1 day 22, before and after histotripsy.
Number of Participants with Increase in Adaptive Immune System Response following histotripsy
Increased adaptive immune system response following histotripsy in addition to ongoing maintenance durvalumab therapy will be interpreted as T cell infiltration, downregulation of myelosuppressive cell types, and upregulation of IFN-γ. This will be completed on the biopsy tissue (pre histotripsy in comparison to post histotripsy).
Percent of Participants Experiencing Immune-mediated Adverse Events within 30 days of histotrispy
Progression Free Survival (PFS)
Overall Survival (OS)
Treatment Efficacy
Treatment Efficacy: defined as the lack of a nodular or mass-like area of enhancement within or along the edge of completed treated tumors assessed via MR or CT imaging at 30-days post procedure
Hepatic toxicity profile of immunotherapy checkpoint with histotripsy reported as Incidence of Dose Limiting Toxicities per Protocol
Hepatic toxicity profile of immunotherapy checkpoint with histotripsy will be assessed using CTCAE version 5 grading and summarized here by number of events.
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University of Wisconsin, Madison
Lead sponsor
HistoSonics, Inc.
Collaborator
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