Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer

Sponsor

Thomas Jefferson University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04821284

Collaborator

(none)

120

Enrollment

Locations

Arms

36.8

Anticipated Duration (Months)

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Optimizing Ultrasound Enhanced Delivery of Therapeutics

Actual Study Start Date :

Dec 6, 2021

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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-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 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
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-paclitaxel, and every 14 days for up to 7 cycles for FOLFIRINOX in the absence of disease progression or unacceptable toxicity.	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

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-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

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

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

Outcome Measures

Primary Outcome Measures

Progression-free survival [Up to 3 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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