A Study Comparing Whole-Body Heat Treatment Plus Systemic Therapy to Systemic Therapy Alone, for Advanced Pancreatic Cancer

Inclusion criteria

• Subjects at least 18 years of age at time of signing the informed consent
• Subjects with metastatic pancreatic adenocarcinoma (PDAC) confirmed by histology
• Measurable disease per RECIST 1.1
• Subjects previously treated with chemotherapy in first line for metastatic disease
• ECOG performance status ≤ 1
• Height ≤ 2,00 m, BMI maximal 40 or positive fitting session
• Adequate liver structure (accessible metastasis-free and functional liver parenchyma) allowing stable liver sensor positioning without unacceptable risks of bleeding and perforation, based on echographic assessment (or any imaging modality)
• Adequate bone marrow function defined as

• white blood cell count ≥ 2000/µl
• neutrophils ≥ 1500 cells/μL
• platelets ≥ 100 x 109/L
• hemoglobin ≥ 9 g/dl (female) and ≥10 g/dl (male) documented
• Adequate coagulation defined as

• PT (%) ≥ 70%
• aPTT ≤ ULN
• Adequate liver function defined as

• Transaminases (AST, ALT) ≤ 2.5 x ULN or ≤ 5.0 in presence of liver metastasis
• bilirubin ≤ 2 x ULN
• Adequate renal function defined as calculated eGFR ≥ 60 mL/min (CKD-EPI equation)
• Normal ionogram
• Effective contraception for both male and female subjects if applicable. Women of childbearing potential must have a negative pregnancy test at screening visit.
• Written informed consent must be given according to good clinical practice and national/local regulations.

Exclusion criteria

• Pregnant or breastfeeding women
• Presence of brain metastasis (known or suspected)
• Other malignant diseases in the medical history during the last 5 years (exceptions: carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin)
• Serious medical risk factors involving any of the major organ systems, including high cardiovascular risk defined as recent major cardiovascular events (such as myocardial infarction or stroke), clinically relevant heart failure due to structural or mechanical cardiac abnormalities (e.g., valvular disease or myocardial dysfunction), and clinically significant arrhythmias.
• Pathology that would interfere with the placement of the bladder catheter
• Clinically significant pulmonary disease which might interfere with mechanical ventilation
• History of autonomic dysfunction (due to the influence on skin blood flow)
• History of malignant hyperthermia
• History of untreated endocrine pathology (e.g. diabetes type II, hyper- or hypothyroidism).
• Primary untreated diabetes type I not related to the oncological condition (due to vascular complications).
• Known allergies to drugs that will be used during the trial (e.g. anesthetic, analgesic, chemotherapy)
• Active infections not controlled by medication
• Presence of clinically significant ascites and/or decompensated cirrhosis/portal hypertension
• Severe, non-healing wounds, ulcers or bone fractures
• Organ allografts requiring immunosuppressive therapy
• Implants that are not compatible with temperature changes
• (History of) clinically significant (investigator decision) psychiatric disorder and/or psychosocial disorder that may interfere with adequate compliance to the protocol or signature of the informed consent
• Other clinically significant disease which could impair the subject's ability to participate in the study according to the investigator's opinion
• Participation in another clinical trial 2 weeks prior to the randomization
• Biological therapy during the 2 weeks prior to the randomization
• Radiotherapy up to 2 weeks prior to the randomization
• Major surgery up to 6 weeks prior to the randomization (port-a-cath placement is minor)