Histotripsy in Biliary Tract Cancer

NCT07853690 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 25-00631
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to examine the safety and feasibility of histotripsy in two cohorts of 12 patients each with Biliary Track Cancer (BTC), with a plan to expand to a larger multi-center study if both safety and feasibility are demonstrated. All patients from cohort 1 will be evaluated for objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) of histotripsy in combination with chemoimmunotherapy. Toxicity profile of histotripsy will be characterized for this cohort. For Cohort 2, in addition to the above evaluations, changes in serum bilirubin levels (total and direct) over time, time to biliary decompression or normalization of bilirubin (total and direct), and percent of patients rendered eligible for chemoimmunotherapy with GCD/P will also be assessed.

Conditions

Biliary Track Cancer

Keywords

BTC

Outcome Measures

Primary Outcomes (3)

• Objective response rate (ORR)

  Objective response rate (ORR) defined as the proportion of patients with a best overall response of either Complete Response (CR) or Partial Response (PR), as determined by standardized imaging criteria (RECIST v1.1)

  up to 24 months

• Incidence of serious adverse events (SAEs)

  Incidence of serious adverse events (SAEs) defined as events that are life-threatening, require hospitalization, result in disability, etc.

  up to 24 months

• Incidence of major procedure-related complications through 30 days post-histotripsy

  Incidence of major procedure-related complications through 30 days post-histotripsy defined as an AE classified as CTCAE grade 3 or higher

  through 30 days post-histotripsy

Secondary Outcomes (11)

• Duration of response (DOR)

  up to 24 months

• Disease control rate (DCR)

  up to 24 months

• Progression free survival (PFS)

  up to 24 months

• Overall survival (OS)

  up to 24 months

• Incidence of treatment-related adverse events (TRAEs)

  up to 24 months

Study Arms (2)

Cohort 1: Patients eligible for chemoimmunotherapy

EXPERIMENTAL

Eligible patients will undergo histotripsy and therapy with GCD/P (gemcitabine 1,000 mg/m2 IV and cisplatin 25 mg/m2 IV days 1 and 8 with durvalumab 1,500 mg IV or pembrolizumab 200 mg IV day 1 in 21-day cycles) until disease progression or intolerable toxicity. Patients will have the option of narrowing to maintenance durvalumab/pembrolizumab with or without gemcitabine after 4-6 months of GCD/P as per standard-of-care.

Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Drug: Pembrolizumab; Device: Histotripsy

Cohort 2: Patients not eligible for chemoimmunotherapy

EXPERIMENTAL

Eligible patients will undergo histotripsy (with or without standard of care biliary tract stenting) and then be monitored with weekly hepatic function panels and clinic visits to monitor status of biliary tract obstruction and for candidacy for chemoimmunotherapy. Patients who become eligible for chemoimmunotherapy will undergo treatment with GCD/P as per Cohort 1 until disease progression or intolerable toxicity following the same peripheral blood and imaging schedule as Cohort 1.

Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Drug: Pembrolizumab; Device: Histotripsy

Interventions

Gemcitabine DRUG

1000 mg/m2 over 30 minutes on Days 1, 8, of each cycle (every 3 weeks), infused according to local labeling.

Cohort 1: Patients eligible for chemoimmunotherapy; Cohort 2: Patients not eligible for chemoimmunotherapy

Cisplatin DRUG

The reconstituted solution should be administered by IV infusion over a 6- to 8-hour period. Cisplatin is given on Days 1 and 8 of each cycle (every 3 weeks), infused according to local labeling

Cohort 1: Patients eligible for chemoimmunotherapy; Cohort 2: Patients not eligible for chemoimmunotherapy

Durvalumab DRUG

Given on day 1 of each cycle (every 3 weeks), infused according to local labeling. Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.

Cohort 1: Patients eligible for chemoimmunotherapy; Cohort 2: Patients not eligible for chemoimmunotherapy

Pembrolizumab DRUG

Given on day 1 of each cycle (every 3 weeks), infused according to local labeling. Administer diluted solution intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter.

Cohort 1: Patients eligible for chemoimmunotherapy; Cohort 2: Patients not eligible for chemoimmunotherapy

Histotripsy DEVICE

Histotripsy is a non-invasive medical technique that uses focused ultrasound waves to mechanically break down and destroy targeted tissues through a process called cavitation.

Cohort 1: Patients eligible for chemoimmunotherapy; Cohort 2: Patients not eligible for chemoimmunotherapy

Eligibility Criteria

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

You may qualify if:

• Both Cohorts
• Age \>/= 18 at time of screening
• Willing and able to provide informed consent for the trial
• Histologically or cytologically confirmed biliary tract cancer (BTC) including cancers of the intrahepatic bile ducts, extrahepatic bile ducts, and gallbladder
• Locally advanced or metastatic disease not eligible for resection or transplant
• RECIST v 1.1 measurable disease
• No prior systemic therapy for the treatment of locally advanced/metastatic disease a. Recurrent disease after surgical resection must have occurred \>/= 6 months from completion of adjuvant therapy
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
• Adequate organ and bone marrow function, defined as:
• Hemoglobin \> 9.0 g/dL
• Absolute neutrophil count \> 1.5 x 109/L
• Platelet count \> 100 x 109/L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN
• Creatinine within normal limits OR measured creatinine clearance (CL) \>50 mL/min OR calculated creatinine clearance (CL) \>50 mL/min as determined by Cockcroft-Gault
• Willing and able to undergo general anesthesia and histotripsy procedure

You may not qualify if:

• Both Cohorts
• Prior exposure to immune-mediated therapy, including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies
• History of allogeneic or solid organ transplant
• Active or prior documented autoimmune disorders. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients with celiac disease controlled by diet alone.
• Patients without active disease in the last 5 years may be included but only after consultation with the study PI.
• Uncontrolled intercurrent illness, including, but not limited to:
• a. Ongoing or active infection including but not limited to the below. Patients on prophylactic antibiotics may be eligible after discussion with the study PI.
• i. Tuberculosis (tuberculosis testing by local institutional practice is required prior to receipt of chemoimmunotherapy) ii. Hepatitis B (HCV) defined as presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥10 IU/mL (testing is required prior to receipt of chemoimmunotherapy).
• \. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and the absence of HBsAg) are eligible.
• iii. Hepatitis C (HCV) defined as positive HCV antibody (testing is required prior to receipt of chemoimmunotherapy).
• \. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Interventions

Gemcitabine; Cisplatin; durvalumab; pembrolizumab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Kristen Spencer, DO, MPH

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen Spencer, DO, MPHDO, MPH

CONTACT

212-731-6667; cancertrials@nyulangone.org

Sandra John-Henry

CONTACT

212-404-4219; Sandra.John-Henry@nyulangone.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: October 2, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Kristen.spencer@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.

Locations

US (1)