Intrahepatic CholangiocarcinomaPhase 2CODAHNCT07766187
Combination Therapy Using Durvalumab and Histotripsy for Treatment of Intrahepatic Cholangiocarcinoma
A Phase 2 study testing Histotripsy, Durvalumab and Biopsy in people with Intrahepatic Cholangiocarcinoma, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intrahepatic Cholangiocarcinoma
- What is being tested?
- Histotripsy, Durvalumab and Biopsy
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Aug 2032
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Renal function: serum creatinine <2x ULN.
- Hematologic function: Absolute neutrophil count >1,000/uL and platelet >50,000/uL, hemoglobin >8.0 g/dL.
- Participant has an International Normalized Ratio (INR) score of <3.0, ≤7 days prior to the planned histotripsy procedure date.
- Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to registration.
- Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from heterosexual vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study and for up to 14 months after the last dose of study drug(s). Males able to father a child must be willing to abstain from heterosexual vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for up to 11 months after the last dose of study drug(s).
- Ability of the participant to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Who cannot join
- 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 not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse effects (exceptions for alopecia, grade 2 neuropathy, grade 2 hypothyroidism, grade 2 hypoadrenalism) related to previous anti-cancer therapy. Please refer to inclusion criteria for lab-based enrollment parameters.
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- 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.
- Untreated central nervous system (CNS) metastasis. Screening of asymptomatic patients for CNS metastasis is not required for enrollment.
- Live vaccine administration within 28 days of planned initial dose of durvalumab.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Wisconsin
Madison, Wisconsin, 53706
About this study
Official title: Combination Therapy Using Durvalumab and Histotripsy for Treatment of Intrahepatic Cholangiocarcinoma (CODAH Trial)
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.
Read the detailed description
The primary objective of this pilot phase II study is to evaluate preliminary efficacy of increased immune system activation and safety of combined histotripsy and maintenance durvalumab therapy.
The secondary objectives are to evaluate additional efficacy signal and safety of the addition of histotripsy along with continued maintenance durvalumab therapy.
Exploratory objectives include evaluation for off-target effects on iCCA tumors not targeted for histotripsy treatment and evaluation of peripheral blood samples for assessment of circulating immune biomarkers and circulating tumor DNA (ctDNA).
- Conditions
- Intrahepatic Cholangiocarcinoma
- Being tested
- Histotripsy, Durvalumab, Biopsy
- Keywords
- iCCA, histotripsy, tumor microenvironment, immunotherapy
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HistotripsyDevice
Also called HistoSonics Edison System
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.
DurvalumabDrug
Also called durvalumab maintenance
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.
BiopsyProcedure or surgery
Two research biopsies are planned for cycle 1 day 3 and cycle 1 day 22, before and after histotripsy.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Histotripsy; Drug: Durvalumab; Procedure: Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Measured: data collected up to day 38 (30 days post-histotripsy)
Secondary outcomes (4)
Progression Free Survival (PFS)
Measured: up to 5 years
Overall Survival (OS)
Measured: up to 5 years
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
Measured: 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
Hepatic toxicity profile of immunotherapy checkpoint with histotripsy will be assessed using CTCAE version 5 grading and summarized here by number of events.
Measured: data collected up to day 38 (30 days post-histotripsy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2026
- Study startOct 2026 (estimated)
- Primary completionAug 2032 (estimated)
- Study completionAug 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- HistoSonics, Inc.
- Responsible party
- Sponsor
- Investigators
- John Swietlik, MD, Principal investigator, UW School of Medicine and Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07766187
- Sponsor's protocol ID
- 2026-0458
- Other IDs
- Protocol Version 5/8/26, SMPH / Radiology
- Acronym
- CODAH
- Status last verified
- Aug 2026
- First submitted
- 20 Jul 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: We would share the following de-identified data with HistoSonics, Inc.: histotripsy data, images, diagnosis, weight, height, age, and gender. The Department of Radiology Medical Imaging Research Support (MIRS) Radius team will serve as an honest broker for the sharing of coded data and images. Results from routine (safety) blood tests and imaging assessments will be placed in participants' EMR.