Development of a Perfusion-induced Systemic Hyperthermia Delivery Apparatus

Period of Performance: 06/02/2011 - 06/30/2011


Phase 2 STTR

Recipient Firm

Exatherm, LLC
Lexington, KY 40506
Principal Investigator


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, clinical vv-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 (42C 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 phase I 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.