Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer

NCT04821284 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 20F.1207R01CA199646JT 15477
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 2

Brief Summary

This phase I/II trial studies the effect of sonoporation in addition to standard of care chemotherapy in treating patients with pancreatic cancer. Sonoporation is a novel method that uses ultrasound and microbubbles to increase therapeutic effect by increasing uptake or enhance sensitization. Sonoporation together with chemotherapy may work better in treating patients with pancreatic cancer compared to chemotherapy alone.

Conditions

Locally Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Unresectable Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Gehan-Breslow-Wilcoxon test and Log-rank (Mantel-Cox) test will be used to compare progression free survival (PSF) between the groups with and without sonoporation.

  Up to 3 years

Secondary Outcomes (5)

• Number of chemotherapy cycles a subject can tolerate

  Up to 3 years

• Overall survival

  Up to 3 years

• Tumor volume changes

  Up to 3 years

• Contrast enhanced ultrasound data

  Up to 3 years

• Tumor stiffness

  Up to 3 years

Study Arms (2)

Arm I (sonazoid, ultrasound, chemotherapy)

EXPERIMENTAL

Patients receive standard of care chemotherapy consisting of gemcitabine hydrochloride and nab-paclitaxel IV over 60 minutes on days 1, 8 and 15 OR FOLFIRINOX IV on days 1 and 2. Treatments repeat every 28 days for up to 3 cycles for gemcitabine and nab-paclitaxel, and every 14 days for up to 7 cycles for FOLFIRINOX in the absence of disease progression or unacceptable toxicity. Patients also receive sonazoid IV over 20 minutes and undergo CEUS. Patients undergo CT or PET/CT or MRI during screening and as clinically indicated on study.

Drug: Gemcitabine Hydrochloride; Drug: Nab-paclitaxel; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Other: Perflubutane Microbubble; Procedure: Contrast-Enhanced Ultrasound; Other: Quality-of-Life Assessment; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Arm II (chemotherapy)

ACTIVE COMPARATOR

Patients receive standard of care chemotherapy consisting of gemcitabine hydrochloride and nab-paclitaxel IV over 60 minutes on days 1, 8 and 15 OR FOLFIRINOX IV on days 1 and 2. Treatments repeat every 28 days for up to 3 cycles for gemcitabine and nab-paclitaxel, and every 14 days for up to 7 cycles for FOLFIRINOX in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT or MRI during screening and as clinically indicated on study.

Drug: Gemcitabine Hydrochloride; Drug: Nab-paclitaxel; Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Other: Quality-of-Life Assessment; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: 1-(2-Oxo-4-amino-1, 2-dihydropyrimidin-1-yl)-2-deoxy-2, 2-difluororibose, hydrochloride, 122111-03-9, 2'Deoxy-2', 2'-Difluorocytidine, Hydrochloride, dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, nanoparticle paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Paclitaxel Nanoparticle Albumin-bound, Paclitaxel Protein-Bound, protein-bound paclitaxel

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Fluorouracil DRUG

Given IV

Also known as: 2,4-Dioxo-5-fluoropyrimidine, 5 Fluorouracil, 5 FU, 5 Fluorouracilum, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluoro-2,4(1H,3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, 5-Fu, 51-21-8, 5FU, AccuSite, Carac, Fluoro Uracil, fluorouraci, Fluouracil, Flurablastin, Fluracedy, Fluracil, Fluril, Ribofluor, Ro 2-9757

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: 136572-09-3, Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Leucovorin Calcium DRUG

Given IV

Also known as: 1492-18-8, 5-Formyl Tetrahydrofolate, 5-Formyl-5,6,7,8-tetrahydrofolic Acid, 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid, Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calcium N-(p-((((6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl)amino)benzoyl)-L-glutamate (1:1), Calfolex, Calinat, Cehafolin, Citofolin, Citrec, citrovorum factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, N-[4-[[(2-Amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amnio]benzoyl]-L-glutamic Acid, Calcium Salt (1:1), N-[p-[[(2-Amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]glutamic Acid, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, 61825-94-3, [(1R,-2R)-1,2-cyclohexanediamine-N,N'][oxalato (2--)-O,O']platinum, [SP-4-2-(1R-trans)]-(1,2,cyclohexanediamine-N, N')[ethanedioato(2--)-O, O']platinum, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, oxalato (1R,2R-cyclohexanediamine)platinum(II), Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669, trans-l DACH oxalatoplatinum, trans-l diaminocyclohexane oxalatoplatinum

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Perflubutane Microbubble OTHER

Oxaliplatin

Arm I (sonazoid, ultrasound, chemotherapy)

Contrast-Enhanced Ultrasound PROCEDURE

Undergo CEUS

Arm I (sonazoid, ultrasound, chemotherapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT SCAN, tomography

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, nuclear magnetic resonance imaging

Arm I (sonazoid, ultrasound, chemotherapy); Arm II (chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Patient must be \>= 18 years old
• Patient has a new diagnosis of PDAC and is scheduled to undergo SoC chemotherapy
• (International Classification of Diseases \[ICD\]-10 C25.0 Malignant neoplasm: Head of pancreas, C25.1: Malignant neoplasm: Body of pancreas, C25.2 Malignant neoplasm: Tail of pancreas, C25.3 Malignant neoplasm: Pancreatic duct and C25.9 Malignant neoplasm: Pancreas, unspecified). Any ICD-10 code in the C25 section (malignant neoplasm of pancreas) will be acceptable
• Histologically verified, locally advanced (stage II/III) or metastatic (stage IV) adenocarcinoma of the pancreas
• The PDAC must be visible on grayscale ultrasound prior to injection of ultrasound contrast
• Must be ambulatory with an ECOG performance status between 0 and 2
• Female patients of child-bearing potential must have a negative urine pregnancy test and use (and agree to continue to use throughout the study) one of the following forms of contraception from the screening Visit until completion of the first study follow-up visit: hormonal (oral, implant or injection) begun \> 15 days prior to the screening visit, barrier (e.g., condom, diaphragm with spermicide), intra-uterine device or vasectomized partner (6 months minimum). Male patients must also agree to practice throughout the study an approved method of birth control.
• \* (Note: To be considered NOT of child-bearing potential, female patients must be postmenopausal \[with amenorrhea for at least 2 years prior to study entry\] or surgically sterile \[bilateral tubal ligation at least 6 months prior to study entry, or of a hysterectomy and/or bilateral oophorectomy\])
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization (ICH)/Good Clinical Practice (GCP), and national/local regulations

You may not qualify if:

• Patient participated in an investigational study within 7 days prior to study entry (or, if longer, within five half-lives of the last dose of any investigational drug
• Patient has severe chronic obstructive pulmonary disease, or pulmonary hypertension or unstable cardiopulmonary conditions
• Patients who are medically unstable. For example:
• Patients on life support or in a critical care unit
• Patients with unstable occlusive disease (e.g., crescendo angina)
• Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia
• Patients with uncontrolled congestive heart failure (New York Heart Association \[NYHA\] class IV)
• Patients with recent cerebral hemorrhage
• Patients who have undergone surgery within 24 hours prior to the study sonographic examination
• Patient with a history of any psychiatric disorder or cognitive impairment that would interfere with participation in the study in the opinion of the investigator
• Patient requires dialysis or has severely impaired renal function, defined as a serum creatinine \>= 1.5 x ULN or calculated creatinine clearance \< 45 mL/min at the screening visit
• Patient has severe impairment of liver function, defined as a serum albumin level =\< 25 g/L and/or a prothrombin time international normalized ratio (INR) \> 2.3 (or activated partial thromboplastin time \[APTT\] \> 6 seconds above the upper limit of normal), or a Child Pugh Score C at the screening visit
• Patients diagnosed with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)
• Patients with a history of anaphylactic allergy to eggs or egg products, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock. (Subjects with non anaphylactic allergies to eggs or egg products may be enrolled in the study, but must be watched carefully for 1 hour following the administration of Sonazoid)
• Patients that are allergic to any other component of Sonazoid

Sponsors & Collaborators

• Flemming Forsberg: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Related Publications (1)

• Adler O, Machado P, Vu T, Forsberg F, Gilja OH, Adam D. Perfusion Assessment in CEUS Imaging for Estimating Pancreatic Cancer Response to Sonoporation-Enhanced Chemotherapy. Ultrason Imaging. 2026 Jan;48(1):36-52. doi: 10.1177/01617346251367758. Epub 2025 Oct 24.

  PMID: 41133726 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes; Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Oxaliplatin; Magnetic Resonance Spectroscopy; X-Rays

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations; Uracil; Pyrimidinones; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Flemming Forsberg, PhD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor - Radiology

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: March 29, 2021
• Study Start: December 6, 2021
• Primary Completion: October 31, 2025
• Study Completion: February 28, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-09

Locations

NO (1); US (1)