Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Bone Density Conservation Agents

Dermatologic Agents

Vitamins

Amino Acids

Gemcitabine

Paclitaxel

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Albumin-Bound Paclitaxel

Oxaliplatin

Calcium

Folic Acid

Camptothecin

Folfirinox

Calcium, Dietary

Coal Tar

Tetrahydrofolates

Formyltetrahydrofolates

Vitamin B Complex

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Hormones

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Glutamic Acid

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.

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.

Gemcitabine Hydrochloride

Nab-paclitaxel

Irinotecan Hydrochloride

Leucovorin Calcium

Perflubutane Microbubble

Contrast-Enhanced Ultrasound

Quality-of-Life Assessment

Computed Tomography

Magnetic Resonance Imaging

Flemming Forsberg, PhD

Odd Gilja

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.

Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer

Optimizing Ultrasound Enhanced Delivery of Therapeutics

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.

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.

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.

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.

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.

Will be measured as shear wave velocity obtained by ultrasound shear wave elastography and will be compared between the groups with and without sonoporation.

National Cancer Institute (NCI)

Flemming Forsberg

Professor - Radiology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer	NCT04821284	Locally Advance... Metastatic Panc... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Gemcitabine Hyd... Nab-paclitaxel Fluorouracil Irinotecan Hydr... Leucovorin Calc... Oxaliplatin Perflubutane Mi... Contrast-Enhanc... Quality-of-Life... Computed Tomogr... Magnetic Resona...	18 Years -	Thomas Jefferson University
Sonoporation and Chemotherapy for the Treatment of Pancreatic Cancer	NCT04821284	Locally Advance... Metastatic Panc... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Gemcitabine Hyd... Nab-paclitaxel Fluorouracil Irinotecan Hydr... Leucovorin Calc... Oxaliplatin Perflubutane Mi... Contrast-Enhanc... Quality-of-Life... Computed Tomogr... Magnetic Resona...	18 Years -	Thomas Jefferson University

Spots Global Cancer Trial Database for perflubutane microbubble