Safety Study of Whole Body Hyperthermia for Advanced Cancer

Study Overview
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Brief Summary
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Millions of patients die of cancer every year. There are several methods to treat cancer, including surgery, chemotherapy, radiotherapy and immunotherapy. Recently, hyperthermia therapy started playing a role in cancer therapy. It has shown effect in animal experiments and clinical practice. The sponsor has developed a novel device to use hyperthermia for advanced cancer. This study is to prove the safety in human patients of this device & therapy and get the first data on efficacy.

Official Title
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A Mono-centric, 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 (TxNxM1) Metastatic Pancreatic Adenocarcinoma Patients

Conditions
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Advanced Cancer, Pancreatic Cancer Metastatic

Intervention / Treatment
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* Device: Whole body hyperthermia
* Drug: Standard of Care (SOC) chemotherapy according to the NCCN guidelines.


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients between 18- and 75-years of age at time of signing the informed consent Patients with advanced solid cancer (for cohort A1, A2 only) or metastatic pancreatic adenocarcinoma confirmed by histology (for cohort B/C/D only) Patients previously treated or under treatment with standard of care treatment (cohort B/C/D only) or patients without treatment options WHO performance status ≤ 1(see appendix V) Maximum waist circumference ≤ 150 cm Weight ≤ 100 kg Height ≤ 1,90 m Adequate liver structure (confirmed by CT scan) allowing the placement of the liver sensor No (prostate) pathology that would interfere with the placement of the bladder catheter Adequate bone marrow function defined as white blood cell count ≥ 2000/µl neutrophils ≥ 1500 cells/μL platelets ≥ 100 x 109/L hemoglobin ≥ 10 g/dl documented within 1 week prior to first treatment 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 Adequate liver function defined as Transaminases (AST, ALT) ≤ 2.5 x ULN or ≤ 5.0 in presence of liver metastasis bilirubin ≤ 2 x ULN documented Adequate renal function defined as serum creatinine ≤ 1.6 mg/dL (male); ≤ 1.3 mg/dL (female); albumin ≥ 30g/L calculated eGFR ≥ 60 mL/min (CKD-EPI equation) documented within 1 week prior to randomization No blood donation 3 months prior to the WBHT treatment No participation in other clinical trial 4 weeks prior to the WBHT treatment No biological therapy 4 weeks prior to the WBHT treatment or during WBHT treatment No surgery 4 weeks prior to the WBHT treatment No radiotherapy 3 weeks prior to the WBHT treatment or during WBHT treatment No chemotherapy 1 week prior to the WBHT treatment (for cohort A/B/C/D) or during WBHT treatment (for Cohort A1/A2) No anti-platelet aggregation medication intake from 5 days prior to the first WBHT treatment until 5 days after the last treatment No anticoagulant medication intake between screening and last follow-up visit. However, if deemed necessary by the investigator, the patient may receive prophylactic Low Molecular Weight Heparin on the day prior to the first WBHT treatment until 10 days after the last WBHT treatment No transdermal patches during participation in the study No piercings (internally or externally)during WBHT treatment Life expectancy of at least 18 weeks Effective contraception for both male and female patients if applicable. Women of childbearing potential must have negative blood 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 (based on HCG levels) 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, coronary stenting or myocardial infarction in the last year 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 or a positive diagnostic test (Caffeine-Halothane Contracture test) in case of family history of malignant hyperthermia. History of untreated endocrine pathology (e.g. diabetes type II, hyper- or hypothyroidism). Primary diabetes type I (due to vascular complications) Known allergies to drugs that will be used during the trial (e.g. anesthetic, analgesic, (chemotherapy used in cohort B/C/D)) Active infections not controlled by medication Severe, non-healing wounds, ulcers or bone fractures Organ allografts requiring immunosuppressive therapy (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 patient's ability to participate in the study according to the investigator's opinion Participation in another clinical trial during this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1<br>Three patients with advanced solid cancer will be subjected to repetitive hyperthermia starting with 2 hours (day 1), 4 hours (day 8) and 6 hours (day 15) | Device: Whole body hyperthermia<br>* Whole body hyperthermia to treat stage IV cancer patients<br>|
| Experimental: Cohort A2<br>One patient with advanced solid cancer will receive 3 hyperthermia treatments of 4 hours per treatment. The next patient with advanced solid cancer will receive 3 hyperthermia treatments of 6 hours per treatment. | Device: Whole body hyperthermia<br>* Whole body hyperthermia to treat stage IV cancer patients<br>|
| Experimental: Cohort B<br>Three pancreatic cancer patients will be subjected to three hyperthermia treatments (2 hours duration per treatment) alone (1st treatment) or in combination with (2nd and 3rd treatment) Standard of Care (SOC) chemotherapy according to the NCCN guidelines. | Device: Whole body hyperthermia<br>* Whole body hyperthermia to treat stage IV cancer patients<br>Drug: Standard of Care (SOC) chemotherapy according to the NCCN guidelines.<br>* Whole body hyperthermia to treat stage IV pancreatic cancer patients combined with standard of care chemotherapy<br>|
| Experimental: Cohort C<br>Three pancreatic cancer patients will be subjected to three hyperthermia treatments (4 hours duration per treatment) alone (1st treatment) or in combination with (2nd and 3rd treatment) Standard of Care (SOC) chemotherapy according to the NCCN guidelines. | Device: Whole body hyperthermia<br>* Whole body hyperthermia to treat stage IV cancer patients<br>Drug: Standard of Care (SOC) chemotherapy according to the NCCN guidelines.<br>* Whole body hyperthermia to treat stage IV pancreatic cancer patients combined with standard of care chemotherapy<br>|
| Experimental: Cohort D<br>Three pancreatic cancer patients will be subjected to three hyperthermia treatments (6 hours duration per treatment) alone (1st treatment) or in combination with (2nd and 3rd treatment) Standard of Care (SOC) chemotherapy according to the NCCN guidelines. | Device: Whole body hyperthermia<br>* Whole body hyperthermia to treat stage IV cancer patients<br>Drug: Standard of Care (SOC) chemotherapy according to the NCCN guidelines.<br>* Whole body hyperthermia to treat stage IV pancreatic cancer patients combined with standard of care chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse device events (ADEs) in relation to the medical device |  | 4 weeks after last treatment | 
| Incidence of related clinically significant abnormalities on electrocardiogram (ECG), vital signs, physical examination and laboratory parameters |  | 4 weeks after last treatment | 
| Incidence of adverse events (AEs) related to WBHT treatment alone or in combination with SOC chemotherapy according to the NCCN guidelines. nab-paclitaxel or gemcitabine alone |  | 4 weeks after last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evolution of CA19-9 (U/ml) | The evolution of this clinically significant biological parameter will be measured compared to baseline | 4 weeks after last treatment | 
| evolution of CEA (ng/ml) | The evolution of this clinically significant biological parameter will be measured compared to baseline | 4 weeks after last treatment | 
| based on the three primary outcome measures, guidance will be drafted for phase II treatment duration in combination with chemotherapy dosing. |  | 4 weeks after last treatment |