<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04467593</url>
  </required_header>
  <id_info>
    <org_study_id>MATTERS 1</org_study_id>
    <nct_id>NCT04467593</nct_id>
  </id_info>
  <brief_title>Safety Study of Whole Body Hyperthermia for Advanced Cancer</brief_title>
  <acronym>MATTERS</acronym>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ElmediX</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ElmediX</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Millions of patients die of cancer every year. There are several methods to treat cancer,&#xD;
      including surgery, chemotherapy, radiotherapy and immunotherapy. Recently, hyperthermia&#xD;
      therapy started playing a role in cancer therapy. It has shown effect in animal experiments&#xD;
      and clinical practice. The sponsor has developed a novel device to use hyperthermia for&#xD;
      advanced cancer. This study is to prove the safety in human patients of this device &amp; therapy&#xD;
      and get the first data on efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 28, 2021</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse device events (ADEs) in relation to the medical device</measure>
    <time_frame>4 weeks after last treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of related clinically significant abnormalities on electrocardiogram (ECG), vital signs, physical examination and laboratory parameters</measure>
    <time_frame>4 weeks after last treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>4 weeks after last treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>evolution of CA19-9 (U/ml)</measure>
    <time_frame>4 weeks after last treatment</time_frame>
    <description>The evolution of this clinically significant biological parameter will be measured compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>evolution of CEA (ng/ml)</measure>
    <time_frame>4 weeks after last treatment</time_frame>
    <description>The evolution of this clinically significant biological parameter will be measured compared to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>based on the three primary outcome measures, guidance will be drafted for phase II treatment duration in combination with chemotherapy dosing.</measure>
    <time_frame>4 weeks after last treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">14</enrollment>
  <condition>Advanced Cancer</condition>
  <condition>Pancreatic Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>Cohort A1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Whole body hyperthermia</intervention_name>
    <description>Whole body hyperthermia to treat stage IV cancer patients</description>
    <arm_group_label>Cohort A1</arm_group_label>
    <arm_group_label>Cohort A2</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care (SOC) chemotherapy according to the NCCN guidelines.</intervention_name>
    <description>Whole body hyperthermia to treat stage IV pancreatic cancer patients combined with standard of care chemotherapy</description>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Patients between 18- and 75-years of age at time of signing the informed consent&#xD;
&#xD;
          2. Patients with advanced solid cancer (for cohort A1, A2 only) or metastatic pancreatic&#xD;
             adenocarcinoma confirmed by histology (for cohort B/C/D only)&#xD;
&#xD;
          3. Patients previously treated or under treatment with standard of care treatment (cohort&#xD;
             B/C/D only) or patients without treatment options&#xD;
&#xD;
          4. WHO performance status ≤ 1(see appendix V)&#xD;
&#xD;
          5. Maximum waist circumference ≤ 150 cm&#xD;
&#xD;
          6. Weight ≤ 100 kg&#xD;
&#xD;
          7. Height ≤ 1,90 m&#xD;
&#xD;
          8. Adequate liver structure (confirmed by CT scan) allowing the placement of the liver&#xD;
             sensor&#xD;
&#xD;
          9. No (prostate) pathology that would interfere with the placement of the bladder&#xD;
             catheter&#xD;
&#xD;
         10. Adequate bone marrow function defined as&#xD;
&#xD;
               1. white blood cell count ≥ 2000/µl&#xD;
&#xD;
               2. neutrophils ≥ 1500 cells/μL&#xD;
&#xD;
               3. platelets ≥ 100 x 109/L&#xD;
&#xD;
               4. hemoglobin ≥ 10 g/dl documented within 1 week prior to first treatment&#xD;
&#xD;
         11. Adequate coagulation defined as&#xD;
&#xD;
               1. PT (%) ≥ 70%&#xD;
&#xD;
               2. aPTT ≤ ULN&#xD;
&#xD;
               3. Von Willebrand Factor Antigen ≥ LLN&#xD;
&#xD;
               4. Von Willebrand Factor Activity ≥ LLN&#xD;
&#xD;
               5. PFA COL/EPI CT ≤ 1.15 ULN&#xD;
&#xD;
               6. PFA COL/ADP CT ≤ 1.15 ULN&#xD;
&#xD;
         12. Adequate liver function defined as&#xD;
&#xD;
               1. Transaminases (AST, ALT) ≤ 2.5 x ULN or ≤ 5.0 in presence of liver metastasis&#xD;
&#xD;
               2. bilirubin ≤ 2 x ULN documented&#xD;
&#xD;
         13. Adequate renal function defined as&#xD;
&#xD;
               1. serum creatinine ≤ 1.6 mg/dL (male); ≤ 1.3 mg/dL (female);&#xD;
&#xD;
               2. albumin ≥ 30g/L&#xD;
&#xD;
               3. calculated eGFR ≥ 60 mL/min (CKD-EPI equation) documented within 1 week prior to&#xD;
                  randomization&#xD;
&#xD;
         14. No blood donation 3 months prior to the WBHT treatment&#xD;
&#xD;
         15. No participation in other clinical trial 4 weeks prior to the WBHT treatment&#xD;
&#xD;
         16. No biological therapy 4 weeks prior to the WBHT treatment or during WBHT treatment&#xD;
&#xD;
         17. No surgery 4 weeks prior to the WBHT treatment&#xD;
&#xD;
         18. No radiotherapy 3 weeks prior to the WBHT treatment or during WBHT treatment&#xD;
&#xD;
         19. No chemotherapy 1 week prior to the WBHT treatment (for cohort A/B/C/D) or during WBHT&#xD;
             treatment (for Cohort A1/A2)&#xD;
&#xD;
         20. No anti-platelet aggregation medication intake from 5 days prior to the first WBHT&#xD;
             treatment until 5 days after the last treatment&#xD;
&#xD;
         21. No anticoagulant medication intake between screening and last follow-up visit.&#xD;
             However, if deemed necessary by the investigator, the patient may receive prophylactic&#xD;
             Low Molecular Weight Heparin on the day prior to the first WBHT treatment until 10&#xD;
             days after the last WBHT treatment&#xD;
&#xD;
         22. No transdermal patches during participation in the study&#xD;
&#xD;
         23. No piercings (internally or externally)during WBHT treatment&#xD;
&#xD;
         24. Life expectancy of at least 18 weeks&#xD;
&#xD;
         25. Effective contraception for both male and female patients if applicable. Women of&#xD;
             childbearing potential must have negative blood pregnancy test at screening visit.&#xD;
&#xD;
         26. Written informed consent must be given according to good clinical practice and&#xD;
             national/local regulations.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Pregnant or breastfeeding women (based on HCG levels)&#xD;
&#xD;
          2. Presence of brain metastasis (known or suspected)&#xD;
&#xD;
          3. Other malignant diseases in the medical history during the last 5 years (exceptions:&#xD;
             carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the&#xD;
             skin)&#xD;
&#xD;
          4. Serious medical risk factors involving any of the major organ systems, including high&#xD;
             cardiovascular risk, coronary stenting or myocardial infarction in the last year&#xD;
&#xD;
          5. Clinically significant pulmonary disease which might interfere with mechanical&#xD;
             ventilation&#xD;
&#xD;
          6. History of autonomic dysfunction (due to the influence on skin blood flow)&#xD;
&#xD;
          7. History of malignant hyperthermia or a positive diagnostic test (Caffeine-Halothane&#xD;
             Contracture test) in case of family history of malignant hyperthermia.&#xD;
&#xD;
          8. History of untreated endocrine pathology (e.g. diabetes type II, hyper- or&#xD;
             hypothyroidism).&#xD;
&#xD;
          9. Primary diabetes type I (due to vascular complications)&#xD;
&#xD;
         10. Known allergies to drugs that will be used during the trial (e.g. anesthetic,&#xD;
             analgesic, (chemotherapy used in cohort B/C/D))&#xD;
&#xD;
         11. Active infections not controlled by medication&#xD;
&#xD;
         12. Severe, non-healing wounds, ulcers or bone fractures&#xD;
&#xD;
         13. Organ allografts requiring immunosuppressive therapy&#xD;
&#xD;
         14. (History of) clinically significant (investigator decision) psychiatric disorder&#xD;
             and/or psychosocial disorder that may interfere with adequate compliance to the&#xD;
             protocol or signature of the informed consent&#xD;
&#xD;
         15. Other clinically significant disease which could impair the patient's ability to&#xD;
             participate in the study according to the investigator's opinion&#xD;
&#xD;
         16. Participation in another clinical trial during this trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc Peeters, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Antwerp</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oleg Rudenko, MD MSc</last_name>
    <phone>+3215262981</phone>
    <email>oleg.rudenko@elmedix.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital Antwerp</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc Peeters, Professor</last_name>
      <phone>+3238213000</phone>
      <email>oncologie@uza.be</email>
    </contact>
    <investigator>
      <last_name>Dirk Ysebaert, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Vera Saldien, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperthermia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04467593
org study id: MATTERS 1
nct id: NCT04467593
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse device events (ADEs) in relation to the medical device
time frame: 4 weeks after last treatment
measure: Incidence of related clinically significant abnormalities on electrocardiogram (ECG), vital signs, physical examination and laboratory parameters
time frame: 4 weeks after last treatment
measure: 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
time frame: 4 weeks after last treatment
measure: evolution of CA19-9 (U/ml)
time frame: 4 weeks after last treatment
description: The evolution of this clinically significant biological parameter will be measured compared to baseline
measure: evolution of CEA (ng/ml)
time frame: 4 weeks after last treatment
description: The evolution of this clinically significant biological parameter will be measured compared to baseline
measure: based on the three primary outcome measures, guidance will be drafted for phase II treatment duration in combination with chemotherapy dosing.
time frame: 4 weeks after last treatment
arm group label: Cohort A1
arm group type: Experimental
description: 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)
arm group label: Cohort A2
arm group type: Experimental
description: 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.
arm group label: Cohort B
arm group type: Experimental
description: 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.
arm group label: Cohort C
arm group type: Experimental
description: 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.
arm group label: Cohort D
arm group type: Experimental
description: 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.
intervention type: Device
intervention name: Whole body hyperthermia
description: Whole body hyperthermia to treat stage IV cancer patients
arm group label: Cohort A1
arm group label: Cohort A2
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort D
intervention type: Drug
intervention name: Standard of Care (SOC) chemotherapy according to the NCCN guidelines.
description: Whole body hyperthermia to treat stage IV pancreatic cancer patients combined with standard of care chemotherapy
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Marc Peeters, MD PhD
role: Principal Investigator
affiliation: University Hospital, Antwerp
last name: Oleg Rudenko, MD MSc
phone: +3215262981
email: oleg.rudenko@elmedix.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Belgium
responsible party type: Sponsor
mesh term: Hyperthermia
sharing ipd: No