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.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- ElmediX
- 入组人数
- 95
- 试验地点
- 4
- 主要终点
- Overall survival (OS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%
- •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.
排除标准
- •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)
结局指标
主要结局
Overall survival (OS)
时间窗: 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
To compare Overall Survival (OS) between WBHT + standard-of-care (SoC) and SoC treatment group
Safety and tolerability of WBHT + SoC and SoC alone
时间窗: From moment of enrollment (ICF signature) up to End of Treatment visit, an (expected) average of 10 months
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.
次要结局
- Progression-free survival (PFS)(Up to time of progression, death or study discontinuation; an (expected) average of 8 months)
- Disease control rate (DCR)(Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months)
- Objective response rate (ORR)(Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months)
- Quality of Life assessments (EORTC-QLQ-C30 version 3)(Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months)
- Quality of Life assessments (QLQ Pan 26)(Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months)
- Evolution of CA19-9(Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months)