Cristin-prosjekt-ID: 680965
Sist endret: 18. februar 2020, 10:40

Cristin-prosjekt-ID: 680965
Sist endret: 18. februar 2020, 10:40
Prosjekt

Optimizing Ultrasound Enhanced Delivery of Therapeutics

prosjektleder

Flemming Forsberg
ved Thomas Jefferson University

prosjekteier / koordinerende forskningsansvarlig enhet

  • Thomas Jefferson University

Tidsramme

Aktivt
Start: 25. august 2016 Slutt: 31. juli 2022

Beskrivelse Beskrivelse

Tittel

Optimizing Ultrasound Enhanced Delivery of Therapeutics

Vitenskapelig sammendrag

Pancreatic cancer is the third most common cancer diagnosed in the United States, with more than 43,000 new cases in 2013. It is the fourth leading cause of cancer-related death in both men and women. Nonetheless, there has been no significant improvement in survival for pancreatic ductal adenocarci- noma (PDAC) patients over the past 30+ years. For this reason, there is a considerable and urgent clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, re- sulting in improved outcomes for patients with PDAC. Our proposal aims at developing contrast-enhanced ultrasound-mediated image-guided drug delivery (CEUS-IGDD) to be that methodology and to translate it from the lab to the clinic. The specific tasks are designed to improve the understanding and methodology for control and monitoring of this IGDD platform, with an initial clinical focus on enhancing the effectiveness of standard chemotherapeutics for treatment of inoperable PDAC. Inherently this project constitutes a multidisciplinary challenge (technological, biological, physical, and medical), and our strategy to address the critical barriers therefore unites an interdisciplinary team of academic and industrial investigators from GE Global Research (GE), Haukeland University Hospital and University of Bergen (together: Bergen), Thomas Jefferson University (TJU), and Rush University Medical Center with more limited efforts by the Israel Institute of Technology and GlaxoSmithKline (GSK). 
Aim 1 will develop tools and methods to ascertain optimal conditions (acoustic regime, bubble type) for maximum drug delivery with minimal application of diagnostic-range acoustic energy. 
Aim 2 utilizes two com- plementary established pancreatic adenocarcinoma mouse models, using human MIA PaCa-2luc (Bergen) and PANC-1 (TJU) cell lines. The efficacy of CEUS-IGDD will be evaluated using biodistribution data and quan- titative imaging methods to monitor treatment response expecting a greater median survival of at least 5 days and a median tumor volume reduction of 50% in the treated group compared to animals receiving drug alone. The main focus of this proposal is Aim 3, where a three year, multi-center clinical trial en- rolling one hundred and twenty (120) patients with metastatic or locally advanced and surgically unresectable PDAC will be conducted at TJU and Bergen. All patients will undergo standard of care chemotherapy, with one-half receiving adjunctive CEUS-IGDD. Patient outcomes will be compared by quantitative ultrasound as- sessment, CT imaging including RECIST criteria, ECOG grade, and immunohistochemistry to assess local progression-free and overall survival with the main endpoint being to increase the number of chemo- therapy cycles by 75% in the IGDD group relative to controls.

Public Health Relevance

Our research plan seeks to develop and evaluate ultrasound-mediated microbubble disruption as a clinically translatable platform for image-guided drug delivery (IGDD). The specific tasks are designed to improve the understanding and methodology for control and monitoring of this IGDD platform, culminating in a multi-center clinical trial focusing on enhancing the effectiveness of standard chemotherapeutics for treatment of inoperable pancreatic adenocarcinoma.

prosjektdeltakere

prosjektleder

Flemming Forsberg

  • Tilknyttet:
    Prosjektleder
    ved Thomas Jefferson University

Ragnhild Haugse

  • Tilknyttet:
    Prosjektdeltaker
    ved Klinisk institutt 2 ved Universitetet i Bergen

Jack Alwin Panapasa

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen

Endre Stigen

  • Tilknyttet:
    Prosjektdeltaker
    ved Institutt for biomedisin ved Universitetet i Bergen

Gorka Ruiz de Garibay

  • Tilknyttet:
    Prosjektdeltaker
    ved Klinisk institutt 2 ved Universitetet i Bergen
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