A monocentric, first-in-human (FIH), safety and preliminary efficacy study of (neo) adjuvant, model-based, whole-body hyperthermia (WBHT) treatment in advanced solid cancer patients or stage IV metastatic pancreatic adenocarcinoma patients.

Abstract

TPS625 Background: Whole-Body Hyperthermia (WBHT) represents the only hyperthermia modality available for patients with disseminated malignancies. The rationale for the treatment of malignant disease by heat is based on a direct cell-killing effect at temperatures in the range of 41– 42°C and driven by a number of reasons. Phase-I mining and phase-I veterinary (dog) clinical study proved the safety of WBHT treatment alone and in combination with standard of care therapy in dogs with cancer. A systematic review addressed clinical trials that used WBHT in pancreatic cancer patients. In these trials, the weighted estimate of the treated population median overall survival was 11.7 compared to 5.6 for the control cohorts. Methods: The is a first in-human, mono-centric, non-randomized trial to establish the safety and preliminary efficacy of WBHT treatment with the TempoCure (medical device) alone in patients with advanced solid cancer (cohort A) or in combination to SOC chemotherapy treatment in patients with stage IV metastatic pancreatic adenocarcinoma (cohort B). The study of 12 to 20 patients is not powered for any statistical analysis. The analysis will be limited to descriptive statistics, considered the doses provided and the extra blood sampling taken at different time points. The treatment is applied under deep anaesthesia in a unit connected to the operating room at the hospital. Cohort A1. Three patients with advanced solid cancer will be subjected to repetitive WBHT starting with 2 hours (day 1), 4 hours (day 8) and 6 hours (day 15) using the TempoCure to keep the patient at a temperature of 41.5°C. The patient’s body temperature will be monitored by specific sensors (liver, oesophageal, rectal and cutaneous). Cohort A2. The highest WBHT duration with acceptable side effects from cohort A1 will be applied to three additional patients with advanced solid cancer, once a week and for 15 days in total. Cohort B1. Three pancreatic cancer patients will be subjected to repetitive WBHT starting with 2 hours (day 1), 4 hours (day 8) and 6 hours (day 15) using the TempoCure to keep the patient at a temperature of 41.5°C and in combination with the standard of care chemotherapy. Cohort B2. The highest WBHT duration with acceptable side effects from cohort B1 will be applied in combination with chemotherapy to three pancreatic cancer patients, once a week and for 15 days in total. Major inclusion criteria are: Adequate liver structure (confirmed by CT scan) allowing the placement of the liver sensor; Adequate coagulation defined as; PT (%) ≥ 70%; aPTT ≤ ULN; Von Willebrand Factor Antigen ≥ LLN; Von Willebrand Factor Activity ≥ LLN; PFA COL/EPI CT ≤ 1.15 ULN; PFA COL/ADP CT ≤ 1.15 ULN. Enrollment to Cohort A1 began in July 2021. Clinical trial information: NCT04467593.