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Development of a Perfusion-induced Systemic Hyperthermia Delivery Apparatus

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2010 / STTR
Agency Tracking Number:
R42CA120616
Solicitation Year:
2010
Solicitation Topic Code:
NCI
Solicitation Number:
PA09-081
Small Business Information
MC3, INC.
3526 W Liberty Rd Ste 100  ANN ARBOR, MI 48103-8872
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2010
Title: Development of a Perfusion-induced Systemic Hyperthermia Delivery Apparatus
Agency: HHS
Contract: 2R42CA120616-02
Award Amount: $1,463,834.00
 

Abstract:

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer-related deaths in men and women. The prognosis for patients with advanced stage non-small cell lung cancer (NSCLC), which accounts for 75% of all new lung cancer cases, is dismal with currently available chemotherapy regimens providing only a 9-12 month median survival. Thus, our long term goal is to develop a more effective treatment for late stage NSCLC. One potential candidate for advanced lung cancer therapy is hyperthermia.Our group developed a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system. In a previous phase I clinical trial, the vv-PISH significantly improved median survival in advanced stage NSCLC patients by 363 days. Although our vv-PISH system functioned adequately in the clinical trial, the vv-PISH system was too complex with a multi-site cannulation and numerous dialysis problems. Our Phase I STTR results showed the feasibility of a simple and inexpensive vv-PISH system in delivering a predictable therapeutic hyperthermia dose. The objective of this Phase II STTR proposal is to establish the feasibility of our finalized vv-PISH circuit to safely deliver therapeutic hyperthermia. Specific Aim 1: To finalize and produce an integrated, clinicalvv-PISH prototype. In this specific aim, our system will be finalized to incorporate new developments and integrate off the shelf components into a vv-PISH prototype suitable for preclinical and clinical testing. We will assemble the: 1) peristaltic roller pump (MC3 pump), 2) adult ECMO heat exchanger (ECMOtherm-II(tm)), 3) hemofilter (Renaflow II(r)), 4) water heater (Hemotherm(r)), and 5) double lumen cannula (Avalon Elite(tm)). Once assembled, we will perform bench testing to confirm that design requirements are met. Specific Aim 2: To determine the temperature control performance and in vivo safety of the clinical vv-PISH circuit. In this specific aim, we will establish the safety and reproducibility of the vv-PISH circuit in achieving the target therapeutic dose (42 C for 120 minutes) in adult swine. We will examine major organ function during hyperthermia, and end organ damage or emboli will be examined in a detailed necropsy. Adult swine will also be monitored for five days after hyperthermia administration. Parameters used to assess the safety of the vv-PISH system will include: 1) survival, 2) multiple organ function, and 3) quality of life. This outcomes study is an essential part of the preclinical testing that must precede the clinical trial. Specific Aim 3: To determine the clinical feasibility of the vv-PISH circuit in a prospective randomized clinical trial. In this specific aim, a phase I clinical trial will be performed to test the clinical feasibility of the vv-PISH circuit. Advanced stage (IIIb or IV) NSCLC patients will be randomized into: 1) standard of care treatment consisting of cisplatin and etoposide chemotherapy with concurrent radiation therapy (n=10) and 2) standard of care therapy followed by systemic hyperthermia treatment via our vv-PISH clinical prototype (n=10). Hyperthermia will be given 2 weeks after the last chemotherapy dose. The impact of this work is that we have developed a new treatment strategy for a relatively unresponsive cancer. PUBLIC HEALTH RELEVANCE: Advanced stage lung cancer, which has a median survival of only 10 months, is present in 75% of all new cases. We developed a new circuit to deliver whole body hyperthermia which significantly increased advanced lung cancer patient survival in a previous phaseI clinical trial. Since our Phase I STTR results showed the feasibility of a more simple and inexpensive hyperthermia delivery system, the goal of this Phase II STTR proposal is to establish the feasibility of our finalized circuit to safely deliver therapeutic hyperthermia.

Principal Investigator:

Joseph B. Zwischenberger
859-323-6013
j.zwische@uky.edu

Business Contact:

Kathryn Osterholxer
734-995-9089
koster@mc3corp.com
Small Business Information at Submission:

MC3, INC.
3550 W LIBERTY RD, STE 3 ANN ARBOR, MI -

EIN/Tax ID: 138266722
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
University Of Kentucky
109 KINKEAD HALL
LEXINGTON, KY 40506-0057
Contact: