Safety Study of Whole Body Hyperthermia for Advanced Cancer

Inclusion criteria:

1. Patients between 18- and 75-years of age at time of signing the informed consent

2. Patients with advanced solid cancer (for cohort A only) or metastatic pancreatic adenocarcinoma confirmed by histology (for cohort B only)

3. Patients previously treated (for cohort A and B) or under treatment with standard of care treatment (cohort B only)

4. WHO performance status ≤ 1(see appendix V)

5. BMI ≤ 32 kg/m2

6. Weight ≤ 100 kg

7. Height ≤ 1,90 m

8. Adequate liver structure (confirmed by CT scan) allowing the placement of the liver sensor

9. No (prostate) pathology that would interfere with the placement of the bladder catheter

10. Adequate bone marrow function defined as

1. white blood cell count ≥ 2000/µl

2. neutrophils ≥ 1500 cells/μL

3. platelets ≥ 100 x 109/L

4. hemoglobin ≥ 10 g/dl documented within 1 week prior to first treatment

11. Adequate coagulation defined as

1. Quick-value ≥ 70% (± 1.15 x ULN)

2. aPTT ≤ 2.5 x ULN, documented within 1 week prior to first treatment

3. Fibrinogen ± 1.15 x ULN

4. D-dimers ± 1.15 x ULN

5. Protein-C ± 1.15 x ULN

6. Factor VIII ± 1.15 x ULN

7. Factor IX ± 1.15 x ULN

8. Von Willebrand Factor ± 1.15 x ULN

12. Adequate liver function defined as

1. Transaminases (AST, ALT) ≤ 2.5 x ULN or ≤ 5.0 in presence of liver metastasis

2. bilirubin ≤ 2 x ULN documented

13. Adequate renal function defined as

1. serum creatinine ≤ 1.6 mg/dL (male); ≤ 1.3 mg/dL (female);

2. albumin ≥ 30g/L

3. calculated eGFR ≥ 60 mL/min (CKD-EPI equation) documented within 1 week prior to randomization

14. No blood donation 3 months prior to the WBHT treatment

15. No participation in other clinical trial 4 weeks prior to the WBHT treatment

16. No biological therapy 4 weeks prior to the WBHT treatment or during WBHT treatment

17. No surgery 4 weeks prior to the WBHT treatment

18. No radiotherapy 3 weeks prior to the WBHT treatment or during WBHT treatment

19. No chemotherapy 1 week prior to the WBHT treatment (for cohort A and B) or during WBHT treatment (for Cohort A)

20. No transdermal patches

21. No piercings (internally or externally)

22. Life expectancy of at least 18 weeks

23. Effective contraception for both male and female patients if applicable. Women of childbearing potential must have negative blood pregnancy test at screening visit.

24. Written informed consent must be given according to good clinical practice and national/local regulations.

Exclusion criteria:

1. Pregnant or breastfeeding women (based on HCG levels)

2. Presence of brain metastasis (known or suspected)

3. 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)

4. Serious medical risk factors involving any of the major organ systems, including high cardiovascular risk, coronary stenting or myocardial infarction in the last year

5. Clinically significant pulmonary disease which might interfere with mechanical ventilation

6. History of autonomic dysfunction (due to the influence on skin blood flow)

7. History of malignant hyperthermia or a positive diagnostic test (Caffeine-Halothane Contracture test) in case of family history of malignant hyperthermia.

8. History of untreated endocrine pathology (e.g. diabetes type II, hyper- or hypothyroidism).

9. Primary diabetes type I (due to vascular complications)

10. Known allergies to drugs that will be used during the trial (e.g. anesthetic, analgesic, (chemotherapy used in cohort B))

11. Active infections not controlled by medication

12. Severe, non-healing wounds, ulcers or bone fractures

13. Organ allografts requiring immunosuppressive therapy

14. (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

15. Other clinically significant disease which could impair the patient's ability to participate in the study according to the investigator's opinion

16. Participation in another clinical trial during this trial