Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Optimizing Ultrasound Enhanced Delivery of Therapeutics

Conditions
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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

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be >= 18 years old Patient has a new diagnosis of inoperable PDAC and is scheduled to undergo SoC chemotherapy (inclusion of patients with human immunodeficiency virus [HIV] or chronic hepatitis B and C will be at the discretion of their treating oncologist based on their ability to tolerate SoC chemotherapy) (International Classification of Diseases [ICD]-10 C25.0 Malignant neoplasm: Body of pancreas, C25.2 Malignant neoplasm: Tail of pancreas and C25.3 Malignant neoplasm: Pancreatic duct) Histologically verified, locally advanced (nonresectable 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]) Hemoglobin > 10 g/dL (prior to enrollment per SoC) Neutrophils (polymorphonuclear leukocytes) > 3.5 x 10^9/L (prior to enrollment per SoC) Platelets (PLT) > 100 x 10^9/L (prior to enrollment per SoC) Bilirubin < 75 umol/L (1.5 x upper limit of normal [ULN]) (prior to enrollment per SoC) Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN (prior to enrollment per SoC) Absolute neutrophil count (ANC) of > 1.5 x 10^9/L (1500mm^3) (prior to enrollment per SoC) 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 Exclusion Criteria: 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 with pulmonary vasculitis or a history of pulmonary emboli 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) at the screening visit 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 Patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment Patient is pregnant or is breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (sonazoid, ultrasound, chemotherapy)<br>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. | Drug: Gemcitabine Hydrochloride<br>* Given IV<br>Drug: Nab-paclitaxel<br>* Given IV<br>Drug: Fluorouracil<br>* Given IV<br>Drug: Irinotecan Hydrochloride<br>* Given IV<br>Drug: Leucovorin Calcium<br>* Given IV<br>Drug: Oxaliplatin<br>* Given IV<br>Other: Perflubutane Microbubble<br>* Oxaliplatin<br>Procedure: Contrast-Enhanced Ultrasound<br>* Undergo CEUS<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>|
| Active Comparator: Arm II (chemotherapy)<br>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. | Drug: Gemcitabine Hydrochloride<br>* Given IV<br>Drug: Nab-paclitaxel<br>* Given IV<br>Drug: Fluorouracil<br>* Given IV<br>Drug: Irinotecan Hydrochloride<br>* Given IV<br>Drug: Leucovorin Calcium<br>* Given IV<br>Drug: Oxaliplatin<br>* Given IV<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Gehan-Breslow-Wilcoxon test and Log-rank (Mantel-Cox) test will be used to compare survival. All clinical variables (e.g., concomitant imaging results, blood tests, etc.) will also be compared between the groups with and without sonoporation. When both types of variables are ordinal or continuous, correlations will be calculated. Continuous data will be analyzed using t-tests, or Mann-Whitney tests. | Up to 3 years |