A Study Comparing Whole-Body Heat Treatment Plus Systemic Therapy to Systemic Therapy Alone, for Advanced Pancreatic Cancer (MATTERS-2)

A Multi-Centric, Randomized, Pivotal Study, Evaluating Efficacy and Safety of Whole-Body Hyperthermia Alongside Standard Systemic Anticancer Therapy in Patients With Metastatic Pancreatic Cancer After Failure of First Line Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and limited treatment options following failure of first-line therapy. Whole-body hyperthermia (WBHT) is a non-invasive treatment approach that raises the body's core temperature under controlled conditions and may enhance the effects of anticancer therapies through multiple biological mechanisms, including improved drug delivery, modulation of the immune response, and increased sensitivity to treatment.

The MATTERS-2 study is a multicentre, randomized clinical trial designed to evaluate the efficacy and safety of WBHT in combination with standard systemic anticancer therapy in patients with metastatic PDAC after failure of first-line treatment. Participants will receive either standard systemic therapy alone or standard systemic therapy combined with WBHT.

The primary objective of the study is to determine whether the addition of WBHT improves clinical outcomes compared with standard therapy alone in terms of overall survival (OS) while maintaining safety. Secondary objectives include other clinical outcomes such as progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). Further, quality of life assessments (QoL) and exploratory biomarker analyses will also be performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma (mPDAC); Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: Standard-of-Care Systemic therapy; Device: Whole-body hyperthermia

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: John-Paul Bogers, Prof. Dr.; Phone Number: +32 474296669; Email: john-paul.bogers@elmedix.com

Study Locations

• Belgium
  • Antwerpen
    • Antwerp, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen (Uza)
      • Principal Investigator: Timon Vandamme, Prof. Dr.
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Algemeen Ziekenhuis Maria Middelares (AZ MM)
      • Principal Investigator: Vincent Bouderez, Dr.
• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28050
      • Hospital Universitario HM Sanchinarro (HM CIOCC)
      • Principal Investigator: Antonio Cubillo, Dr.
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
      • Principal Investigator: Mariano Ponz, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects at least 18 years of age at time of signing the informed consent
2. Subjects with metastatic pancreatic adenocarcinoma (PDAC) confirmed by histology
3. Measurable disease per RECIST 1.1
4. Subjects previously treated with chemotherapy in first line for metastatic disease
5. ECOG performance status ≤ 1
6. Height ≤ 2,00 m, BMI maximal 40 or positive fitting session
7. 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)

8. 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 ≥ 9 g/dl (female) and ≥10 g/dl (male) documented

9. Adequate coagulation defined as

   1. PT (%) ≥ 70%
   2. aPTT ≤ ULN

10. 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
11. Adequate renal function defined as calculated eGFR ≥ 60 mL/min (CKD-EPI equation)
12. Normal ionogram
13. Effective contraception for both male and female subjects if applicable. Women of childbearing potential must have a negative pregnancy test at screening visit.
14. Written informed consent must be given according to good clinical practice and national/local regulations.

Exclusion Criteria:

1. Pregnant or breastfeeding women
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 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.
5. Pathology that would interfere with the placement of the bladder catheter
6. Clinically significant pulmonary disease which might interfere with mechanical ventilation
7. History of autonomic dysfunction (due to the influence on skin blood flow)
8. History of malignant hyperthermia
9. History of untreated endocrine pathology (e.g. diabetes type II, hyper- or hypothyroidism).
10. Primary untreated diabetes type I not related to the oncological condition (due to vascular complications).
11. Known allergies to drugs that will be used during the trial (e.g. anesthetic, analgesic, chemotherapy)
12. Active infections not controlled by medication
13. Presence of clinically significant ascites and/or decompensated cirrhosis/portal hypertension
14. Severe, non-healing wounds, ulcers or bone fractures
15. Organ allografts requiring immunosuppressive therapy
16. Implants that are not compatible with temperature changes
17. (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
18. Other clinically significant disease which could impair the subject's ability to participate in the study according to the investigator's opinion
19. Participation in another clinical trial 2 weeks prior to the randomization
20. Biological therapy during the 2 weeks prior to the randomization
21. Radiotherapy up to 2 weeks prior to the randomization
22. Major surgery up to 6 weeks prior to the randomization (port-a-cath placement is minor)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Participants receive standard-of-care systemic treatment as indicated for metastatic pancreatic ductal adenocarcinoma (mPDAC, stage IV) after failure of the first-line treatment.	Drug: Standard-of-Care Systemic therapy; Standard-of-care systemic therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC, stage IV) after failure of first-line treatment.
Experimental: Whole-body hyperthermia treatment (WBHT) group; Participants will receive whole-body hyperthermia (WBHT) alongside their indicated standard-of-care systemic treatment.	Drug: Standard-of-Care Systemic therapy; Standard-of-care systemic therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC, stage IV) after failure of first-line treatment.; Device: Whole-body hyperthermia; Initially every 2 weeks, until a total of 3 treatments is reached. Thereafter every 4 weeks. The treatment will raise the body temperature to 41,50 °C for a total of 4 hours.; Other Names: WBH; WBHT; Systemic hyperthermia; Whole-body thermal treatment; WBTT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To compare Overall Survival (OS) between WBHT + standard-of-care (SoC) and SoC treatment group	From randomization until death from any cause, assessed up to study completion (primary analysis triggered upon occurrence of 66 death events), an (expected) average of 12 months
Safety and tolerability of WBHT + SoC and SoC alone	Incidence of Adverse Events (AE), Serious Adverse Events (SAE), treatment-related AE/SAE and Adverse Device Effects (ADE). They will be reported from moment of enrollment (ICF signature) up to End of Treatment visit and will be assessed for seriousness, severity and relationship to the device and to WBHT treatment.	From moment of enrollment (ICF signature) up to End of Treatment visit, an (expected) average of 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	To compare Progression-Free Survival (PFS) between WBHT +SoC and SoC treatment group based on RECIST 1.1. criteria.	Up to time of progression, death or study discontinuation; an (expected) average of 8 months
Disease control rate (DCR)	To compare Disease Control Rate (DCR) between WBHT +SoC and SoC treatment group based on RECIST 1.1 criteria.	Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months
Objective response rate (ORR)	To compare Objective Response Rate (ORR) between WBHT +SoC and SoC treatment group based on RECIST 1.1 criteria and further described with duration of response (DOR) and time to response (TTR).	Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months
Quality of Life assessments (EORTC-QLQ-C30 version 3)	Quality of Life (QoL) according to EORTC-QLQ-C30 version 3 scoring changes from baseline (at 4-weeks, 8-weeks and End of Treatment)	Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months
Quality of Life assessments (QLQ Pan 26)	Quality of Life (QoL) according to QLQ Pan 26 scoring changes from baseline (at 4-weeks, 8-weeks and End of Treatment)	Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months
Evolution of CA19-9	To evaluate CA19-9 changes from baseline in WBHT +SoC and SoC treatment groups (at 4-weeks, 8-weeks and End of Treatment)	Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analyses	To explore potential biomarkers and molecular correlates through the analysis of blood and tumor tissue samples.	Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months

Collaborators and Investigators

• Sponsor: ElmediX
• Collaborators: Xper research

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Medical device; Hyperthermia
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperthermia
• Other Study ID Numbers: CIV-26-06-058215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No