Combination Therapy Using Durvalumab and Histotripsy for Treatment of Intrahepatic Cholangiocarcinoma

NCT07766187 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: 2026-0458Protocol Version 5/8/26SMPH / Radiology
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

iCCA; histotripsy; tumor microenvironment; immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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).

  data collected cycle 1 day 3 (C1D3) and cycle 1 day 22 (C1D22) (up to about 30 days with allowable procedural windows)

• Percent of Participants Experiencing Immune-mediated Adverse Events within 30 days of histotrispy

  data collected up to day 38 (30 days post-histotripsy)

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  up to 5 years

• Overall Survival (OS)

  up to 5 years

• Treatment Efficacy

  data collected up to day 38 (30 days post-histotripsy)

• Hepatic toxicity profile of immunotherapy checkpoint with histotripsy reported as Incidence of Dose Limiting Toxicities per Protocol

  data collected up to day 38 (30 days post-histotripsy)

Study Arms (1)

Participants with advanced iCCA

EXPERIMENTAL

3 research specific visits; pre-histotripsy treatment (C1D3), 14-day post histotripsy follow-up with biopsy (C1D22), and 30-day post histotripsy treatment adverse events assessment. The remaining visits, including the histotripsy treatment and durvalumab infusions, are a part of the study protocol but are part of the patient's ongoing medical care. Participants followed until progression up to 5 years.

Device: Histotripsy; Drug: Durvalumab; Procedure: Biopsy

Interventions

Histotripsy DEVICE

Histotripsy 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.

Also known as: HistoSonics Edison System

Participants with advanced iCCA

Durvalumab DRUG

Durvalumab 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.

Also known as: durvalumab maintenance

Participants with advanced iCCA

Biopsy PROCEDURE

Two research biopsies are planned for cycle 1 day 3 and cycle 1 day 22, before and after histotripsy.

Participants with advanced iCCA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 has iCCA tumor burden appropriate for biopsy and histotripsy treatment
• Participant able to undergo liver biopsy of Index Tumor.
• Index Tumor will be a predetermined non-histotripsy tumor in patients with multifocal disease, or a predetermined region of intentionally untreated tumor in patients with solitary disease.
• Participant to have iCCA deemed targetable for histotripsy.
• Participants with solitary tumor must have longest dimension ≥ 2.0 cm to allow for planned region of intentionally untreated Target Tumor for Index Tumor.
• Participants' iCCA is considered unresectable or patient is a non-surgical candidate
• Participant can undergo general anesthesia.
• Participant has a Child-Pugh Score of A or B (up to B8).
• Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening.
• Participant meets the following functional criteria, ≤7 days prior to the planned histotripsy procedure date
• Liver function: Alanine transaminase (ALT) and Aspartate transaminase (AST) \<2.5x upper limit of normal (ULN) and/or bilirubin \<2.5 ULN.

You may not qualify if:

• 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. .
• Participant has major surgical procedure or significant traumatic injury ≤2 weeks prior to the planned treatment or not fully recovered (CTCAE grade 1 or better) from side effects/complications of such procedure or trauma.
• Participant has a history of bleeding disorders (e.g. von Willebrand disease) or subject is suspected to have a bleeding disorder.
• Participant has uncorrectable coagulopathy.
• In the opinion of the Investigator, histotripsy is not a treatment option for the subject.
• Participant has a concurrent condition that, in the investigator's opinion, could jeopardize the safety of the subject or compliance with the protocol.
• Participants' tumor(s) is not targetable per discretion of radiologist.
• Participant has a known sensitivity to contrast media and cannot be adequately pre-medicated.
• Participants' Target Tumor(s) has/have had prior locoregional therapy (e.g. ablation, embolization, radiation).
• History of solid organ or allogeneic bone marrow transplantation.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
• Significant dementia or other mental condition that precludes the participant's ability to consent to the study.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• HistoSonics, Inc.: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

durvalumab; Biopsy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• John Swietlik, MD

  UW School of Medicine and Public Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: August 14, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2032
• Study Completion (Estimated): August 1, 2032
• Last Updated: August 14, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (1)