Sonoporation And Chemotherapy For The Treatment Of Pancreatic Cancer

Study Overview

Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer

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.

PRIMARY OBJECTIVE: I. To evaluate the safety and therapeutic efficacy of sonoporation on pancreatic ductal adenocarcinoma (PDAC) standard of care (SoC) treatment based on local progression-free and overall survival with the main endpoint being an increase in median progression-free survival of subjects by 8.7 months in the sonoporation group relative to controls. SECONDARY OBJECTIVES: I. To evaluate the effect of sonoporation on the median time to treatment failure (TTF) (in percent). II. To evaluate the effect of sonoporation on the number of chemotherapy cycles subjects can undergo. III. To evaluate the effect of sonoporation on tumor volume measured by clinical diagnostic ultrasound. IV. To evaluate the effect of sonoporation on tumor perfusion using contrast enhanced ultrasound (CEUS) - specifically harmonic imaging (HI) and subharmonic imaging (SHI). V. To evaluate the effect of sonoporation on tumor interstitial fluid pressures using subharmonic aided pressure estimation (SHAPE). VI. To evaluate the effect of sonoporation on tumor volume using clinical diagnostic computed tomography (CT). VII. To evaluate the effect of sonoporation on tumor stiffness using clinical ultrasound shear wave elastography (SWE). VIII. To evaluate the effect of sonoporation on serum CA 19-9 concentrations. IX. Clinical benefit response, which is a measure of clinical improvement based on analgesic consumption, Eastern Cooperative Oncology Group (ECOG) performance status, and weight change. X. To evaluate the effect of sonoporation on patient quality of life. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard of care chemotherapy consisting of gemcitabine hydrochloride and nab-paclitaxel intravenously (IV) over 60 minutes on days 1, 8 and 15 OR fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (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 computed tomography (CT) or positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) during screening and as clinically indicated on study. ARM II: 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. After completion of study treatment, patients are followed up every 3 months.

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

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

20F.1207
R01CA199646 (U.S. NIH Grant/Contract)
JT 15477 (OTHER Identifier) (OTHER: JeffTrial Number)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-03-26	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-16
First Submitted that Met QC Criteria 2021-03-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-22
First Posted (ACTUAL) 2021-03-29	Results First Posted N/A	Last Verified 2025-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm I (sonazoid, ultrasound, chemotherapy) 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-p	DRUG: Gemcitabine Hydrochloride Given IV DRUG: Nab-paclitaxel Given IV DRUG: Fluorouracil Given IV DRUG: Irinotecan Hydrochloride Given IV DRUG: Leucovorin Calcium Given IV DRUG: Oxaliplatin Given IV OTHER: Perflubutane Microbubble Oxaliplatin PROCEDURE: Contrast-Enhanced Ultrasound Undergo CEUS OTHER: Quality-of-Life Assessment Ancillary studies PROCEDURE: Computed Tomography Undergo CT or PET/CT PROCEDURE: Magnetic Resonance Imaging Undergo MRI
ACTIVE_COMPARATOR: Arm II (chemotherapy) 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-p	DRUG: Gemcitabine Hydrochloride Given IV DRUG: Nab-paclitaxel Given IV DRUG: Fluorouracil Given IV DRUG: Irinotecan Hydrochloride Given IV DRUG: Leucovorin Calcium Given IV DRUG: Oxaliplatin Given IV OTHER: Quality-of-Life Assessment Ancillary studies PROCEDURE: Computed Tomography Undergo CT or PET/CT PROCEDURE: Magnetic Resonance Imaging Undergo MRI

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm I (sonazoid, ultrasound, chemotherapy)

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-p

DRUG: Gemcitabine Hydrochloride

Given IV

DRUG: Nab-paclitaxel

Given IV

DRUG: Fluorouracil

Given IV

DRUG: Irinotecan Hydrochloride

Given IV

DRUG: Leucovorin Calcium

Given IV

DRUG: Oxaliplatin

Given IV

OTHER: Perflubutane Microbubble

Oxaliplatin

PROCEDURE: Contrast-Enhanced Ultrasound

Undergo CEUS

OTHER: Quality-of-Life Assessment

Ancillary studies

PROCEDURE: Computed Tomography

Undergo CT or PET/CT

PROCEDURE: Magnetic Resonance Imaging

Undergo MRI

ACTIVE_COMPARATOR: Arm II (chemotherapy)

DRUG: Gemcitabine Hydrochloride

Given IV

DRUG: Nab-paclitaxel

Given IV

DRUG: Fluorouracil

Given IV

DRUG: Irinotecan Hydrochloride

Given IV

DRUG: Leucovorin Calcium

Given IV

DRUG: Oxaliplatin

Given IV

OTHER: Quality-of-Life Assessment

Ancillary studies

PROCEDURE: Computed Tomography

Undergo CT or PET/CT

PROCEDURE: Magnetic Resonance Imaging

Undergo MRI

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Number of chemotherapy cycles a subject can tolerate	Gehan-Breslow-Wilcoxon test and Log-rank (Mantel-Cox) test will be used to compare number of chemotherapy cycles between the groups with and without sonoporation.	Up to 3 years
Overall survival	Gehan-Breslow-Wilcoxon test and Log-rank (Mantel-Cox) test will be used to compare overall survival (PSF) between the groups with and without sonoporation.	Up to 3 years
Tumor volume changes	Relative changes will be measured with ultrasound, computed tomography and/or magnetic resonance imaging and will also be compared between the groups with and without sonoporation.	Up to 3 years
Contrast enhanced ultrasound data	Will provide perfusion and pressure estimates, which will be compared (individually and jointly) to subject outcomes in the groups with and without sonoporation as determined by the medical oncology team.	Up to 3 years
Tumor stiffness	Will be measured as shear wave velocity obtained by ultrasound shear wave elastography and will be compared between the groups with and without sonoporation.	Up to 3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Flemming Forsberg, PhD

Phone Number: 215-955-4870

Email: flemming.forsberg@jefferson.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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
Any reason why, in the opinion of the investigator, the patient should not participate
Patient is pregnant or is breast-feeding

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Flemming Forsberg, PhD, Thomas Jefferson University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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