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Potential of Moderate Whole Body Hyperthermia to Enhance Response (POWER)

Primary Purpose

Oncology

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
moderate Whole Body Hyperthermia (mWBH)
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oncology

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The general condition of the patients must be sufficient for multimodal treatment (corresponding to WHO status 0-2) Tumordisease in a palliative setting of the following 6 groups: Malignant melanoma, treatment-naive stage IV with multiple metastases and missing BRAF-V600 mutation. With indication for initiation of immunotherapy using PD-1 and CTLA-4 antibody therapy. Patients with metastatic or inoperable pancreatic cancer, who are planning first-line chemotherapy with FOLFIRINOX is. Patients with an indication for palliative radiation therapy extracranial, tumor manifestation with a prescribed radiation dose of 30 to 36 Gy due to hormone receptor-positive carcinoma of the breast, patients must have at least one additional (marker) lesion not treated with radiation. Patients with metastatic high-grade sarcoma for whom metastasis-directed ablative therapy methods are not possible and palliative first-line therapy with doxorubicin. Patients with metastatic or loco-regionally recurrent HPV-associated squamous cell carcinoma (of the head and neck region, cervix, anus or vulva) for whom local therapies are not possible and for whom palliative first-line therapy containing platinum is planned. Patients with metastatic, castration-resistant prostate cancer, with progressive disease after exceeding the recommended therapy options for which a therapy attempt with lutetium-177-PSMA was indicated. Exclusion Criteria: Presence of contraindications to simultaneous chemotherapy or whole-body hyperthermia Serious or active comorbidities that could interfere with treatment or understanding of the nature and content of the study, for example: Chronic inflammatory bowel disease Acute infections Serious cardiovascular or pulmonary comorbidities Mental illnesses, showing the proper Study participation or recording the nature of the study to make impossible Presence of cerebral metastasis Diabetes mellitus with risk of end-organ damage

Sites / Locations

  • Klinik für Radioonkologie und StrahlentherapieRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

mWBH

Control group

Arm Description

patients receiving moderate Whole Body Hyperthermia

Patients do not receive moderate Whole Body Hyperthermia

Outcomes

Primary Outcome Measures

change in the number of circulating tumor cells before therapy vs after therapy
ANCOVA is used as the statistical methodology. The change in the number of circulating tumor cells three months after the start of therapy is the dependent variable, the group (intervention or control) and the number of circulating tumor cells as well as the tumor entity (6 groups) are independent variables. Case number estimation: So far there are no studies that have examined this outcome. We assume that the intervention effect is moderate and that an effect size of 0.6 to 0.7 can be achieved. If 36 patients per arm are included in the study, an effect size (Cohen's d) of 0.67 or greater at a two-sided significance level of α=0.05 with a power of 80% can be demonstrated using the t-test for independent samples.

Secondary Outcome Measures

Response of the tumors
morphologically in imaging
Quality of life of the patients
The hypothesis is that patients with mWBH report a higher quality of life than patients without mWBH. Life Quality will be assessed in a standardized questionnaire as EORTC QLQ-30
influence of mWBH on depressive/dysthymic moods/episodes as well as on fatigue symptoms
reported by patients in standardized questionnaire
impact of patient-reported organ-specific functional impairment
measured by standardized questionnaires (depending tumor entity e.g. PR25 in patients with prostate cancer, BR23 in breast cancer, MEL38 in melanoma, and PAN26 in pancreatic cancer
influence of mWBH on different leukocyte sub-populations and the plasma concentration of cytokines/proteins, which indicate a suspected predictive effect on the response to immunotherapy.
leukocyte sub-populations are measured by FACS
side effect profile of mWBH
side effects reported by practitioner and the patient, potential side effects will be documented in Case Report Form (CRF) which will be filled out in follow up visits
Tumor marker responses in patients who have measurable tumor markers that have previously also been correlated with disease activity
It is assumed that this is the case in a total of 50 patients (ITT) (25 in each group)
survival rate and rate of progression-free surviving patients across all stratification groups.
PFS = death or any form of tumor recurrence, local or systemic, are counted as an event here
The impact of mWBH on leukocyte nadir and time to recovery in patients receiving radiation, lutetium, or cytostatic therapy (arms 2-6)
Comparison of routine lab-testing within intervention group and between control
In arm 3 (breast cancer): The influence of mWBH on the occurrence of an abscopal effect, i.e. a response of a tumor lesion outside the irradiated volume (dose < 4 Gray during fractionated palliative irradiation)
Response is evaluated by the RECIST criteria: CR or PR

Full Information

First Posted
February 7, 2023
Last Updated
April 6, 2023
Sponsor
Charite University, Berlin, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT05821166
Brief Title
Potential of Moderate Whole Body Hyperthermia to Enhance Response
Acronym
POWER
Official Title
Moderate Whole-body Hyperthermia in Tumor Patients: Influence on Circulating Tumor Cells, Tumor Response, Quality of Life, Fatigue, Psyche, Immune Response and Tumor Microenvironment
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
December 1, 2026 (Anticipated)
Study Completion Date
December 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Using moderate whole-body hyperthermia (mWBH) in tumor patients to see the influence on circulating tumor cells, tumor response, quality of life, fatigue, psyche, immune response and tumor microenvironment
Detailed Description
Moderate whole-body hyperthermia (mWBH) is considered to be a very well-tolerated treatment. It has been used in numerous naturopathic and oncological practices for decades. It is also being used more and more with an increasing number of non-oncological diseases. A recently published randomized study was able to prove a sustained positive effect of whole-body hyperthermia in patients with depressive episodes. However, there are no clinical studies that demonstrate the benefit of this measure with regard to oncological treatment. There is also a lack of clarity about the mechanism of action of mWBH. A positive modification of the tumor microenvironment (increased perfusion, reduced interstitial pressure) and an increased activation of tumor-killing immune cells could be shown preclinically - however, a clinical evaluation of these mechanisms has not yet taken place. This randomized study aims to evaluate the effect of mWBH on the tumor response of patients suffering from advanced cancer. The aim of the study is to demonstrate an improvement in the therapy response rate three months after the end of therapy through the additional use of mWBH, measured by a positive influence on the change in the number of circulating tumor cells from the time before therapy to the time three months after the start of therapy. Quality of life reported by patients, recorded by the FACT-G questionnaire, as well as psychological parameters, fatigue and various other parameters with regard to an increase in the effect on the tumor are evaluated as secondary endpoints. All patients also receive serial immune monitoring. For this purpose, blood samples are taken before therapy and several times during the course of the therapy, which are then evaluated with regard to cytokines, immunological proteins and specific subgroups of immune cells. The patients all receive guideline-based therapy in line with current internal practice. In addition to standard therapy, patients are randomized 1:1 and, if randomized to the mWBH arm, receive an additional 3-4 mWBH sessions during their oncological treatment. A total of six different patient groups are included, all with palliative therapy intentions (patients with multiple metastatic malignant melanoma before initiation of immunotherapy (checkpoint blockade), patients with metastatic or inoperable pancreatic carcinoma for whom first-line chemotherapy with FOLFIRINOX is planned, patients before palliative radiation therapy for a hormone-receptor-positive breast cancer who have previously received palliative systemic therapy and have at least one other tumor lesion in addition to the one that was irradiated, patients with metastatic sarcoma in whom ablation of the metastases is not possible and who are receiving palliative first-line therapy using Doxorubicin is planned to treat patients with metastatic or loco-regionally recurrent HPV-associated squamous cell carcinoma of the head and neck region, cervix, anus or vulva, for whom no local therapy methods are possible and palliative first-line platinum therapy is planned, patients with metastatic castration-resistant prostate cancer with progressive disease after exhaustion of recommended therapy options for whom a therapeutic trial with lutetium-177-PSMA has been indicated). A total of at least 72 patients, stratified into the 6 subgroups mentioned above, should be evaluated in the study, who should receive three to four sessions of mWBH in addition to standard oncological treatment. In order to obtain the necessary minimum number of patients in all subgroups, the inclusion of 80 patients in the study is necessary with an expected drop-out rate of 10%. In order to record the effect of mWBH on quality of life, fatigue and depression, study participants must fill out a questionnaire on quality of life, fatigue and depression before the start of therapy, at the end of treatment and two weeks after therapy. To evaluate the influence of mWBH on immune parameters, patients also receive additional blood samples before the start of therapy, at the end of therapy and at two follow-up times, which can normally be combined with routine blood samples. For further risk stratification, the samples obtained after an operation or biopsy can be used for further analysis. This examination means no additional intervention and no increased risk for the patient, since these have already been carried out routinely. Patients have the option of expressly agreeing to the removal and further use of these biomarkers or rejecting them as part of the declaration of consent.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oncology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomization into intervention group (additional MWB-HT) and standard care (chemotherapy / immunotherapy) and control group (no MWB-HT), only standard care
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
mWBH
Arm Type
Experimental
Arm Description
patients receiving moderate Whole Body Hyperthermia
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Patients do not receive moderate Whole Body Hyperthermia
Intervention Type
Device
Intervention Name(s)
moderate Whole Body Hyperthermia (mWBH)
Intervention Description
Patients receiving 3-4 times mWBH
Primary Outcome Measure Information:
Title
change in the number of circulating tumor cells before therapy vs after therapy
Description
ANCOVA is used as the statistical methodology. The change in the number of circulating tumor cells three months after the start of therapy is the dependent variable, the group (intervention or control) and the number of circulating tumor cells as well as the tumor entity (6 groups) are independent variables. Case number estimation: So far there are no studies that have examined this outcome. We assume that the intervention effect is moderate and that an effect size of 0.6 to 0.7 can be achieved. If 36 patients per arm are included in the study, an effect size (Cohen's d) of 0.67 or greater at a two-sided significance level of α=0.05 with a power of 80% can be demonstrated using the t-test for independent samples.
Time Frame
Test therapy naive versus three months after the start of therapy
Secondary Outcome Measure Information:
Title
Response of the tumors
Description
morphologically in imaging
Time Frame
three months after the start of therapy
Title
Quality of life of the patients
Description
The hypothesis is that patients with mWBH report a higher quality of life than patients without mWBH. Life Quality will be assessed in a standardized questionnaire as EORTC QLQ-30
Time Frame
measured before and 2 weeks after the end of therapy (end of therapy is determined as the last planned mWBH session) or at a comparable time in the control group
Title
influence of mWBH on depressive/dysthymic moods/episodes as well as on fatigue symptoms
Description
reported by patients in standardized questionnaire
Time Frame
Follow-up visits, in total 2 years follow up time
Title
impact of patient-reported organ-specific functional impairment
Description
measured by standardized questionnaires (depending tumor entity e.g. PR25 in patients with prostate cancer, BR23 in breast cancer, MEL38 in melanoma, and PAN26 in pancreatic cancer
Time Frame
Follow-up visits, in total 2 years follow up time
Title
influence of mWBH on different leukocyte sub-populations and the plasma concentration of cytokines/proteins, which indicate a suspected predictive effect on the response to immunotherapy.
Description
leukocyte sub-populations are measured by FACS
Time Frame
measurement before treatment compared with the one after treatment
Title
side effect profile of mWBH
Description
side effects reported by practitioner and the patient, potential side effects will be documented in Case Report Form (CRF) which will be filled out in follow up visits
Time Frame
during and after treatment in Follow-up visits, in total 2 years follow up time
Title
Tumor marker responses in patients who have measurable tumor markers that have previously also been correlated with disease activity
Description
It is assumed that this is the case in a total of 50 patients (ITT) (25 in each group)
Time Frame
measurement before treatment compared with the one after treatment
Title
survival rate and rate of progression-free surviving patients across all stratification groups.
Description
PFS = death or any form of tumor recurrence, local or systemic, are counted as an event here
Time Frame
1 and 2-year
Title
The impact of mWBH on leukocyte nadir and time to recovery in patients receiving radiation, lutetium, or cytostatic therapy (arms 2-6)
Description
Comparison of routine lab-testing within intervention group and between control
Time Frame
during and after treatment in blood assessment
Title
In arm 3 (breast cancer): The influence of mWBH on the occurrence of an abscopal effect, i.e. a response of a tumor lesion outside the irradiated volume (dose < 4 Gray during fractionated palliative irradiation)
Description
Response is evaluated by the RECIST criteria: CR or PR
Time Frame
in follow-up routine imaging controls ( e.g. 3 months after treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The general condition of the patients must be sufficient for multimodal treatment (corresponding to WHO status 0-2) Tumordisease in a palliative setting of the following 6 groups: Malignant melanoma, treatment-naive stage IV with multiple metastases and missing BRAF-V600 mutation. With indication for initiation of immunotherapy using PD-1 and CTLA-4 antibody therapy. Patients with metastatic or inoperable pancreatic cancer, who are planning first-line chemotherapy with FOLFIRINOX is. Patients with an indication for palliative radiation therapy extracranial, tumor manifestation with a prescribed radiation dose of 30 to 36 Gy due to hormone receptor-positive carcinoma of the breast, patients must have at least one additional (marker) lesion not treated with radiation. Patients with metastatic high-grade sarcoma for whom metastasis-directed ablative therapy methods are not possible and palliative first-line therapy with doxorubicin. Patients with metastatic or loco-regionally recurrent HPV-associated squamous cell carcinoma (of the head and neck region, cervix, anus or vulva) for whom local therapies are not possible and for whom palliative first-line therapy containing platinum is planned. Patients with metastatic, castration-resistant prostate cancer, with progressive disease after exceeding the recommended therapy options for which a therapy attempt with lutetium-177-PSMA was indicated. Exclusion Criteria: Presence of contraindications to simultaneous chemotherapy or whole-body hyperthermia Serious or active comorbidities that could interfere with treatment or understanding of the nature and content of the study, for example: Chronic inflammatory bowel disease Acute infections Serious cardiovascular or pulmonary comorbidities Mental illnesses, showing the proper Study participation or recording the nature of the study to make impossible Presence of cerebral metastasis Diabetes mellitus with risk of end-organ damage
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sebastian Zschaeck, MD
Phone
030450650764
Email
sebastian.zschaeck@charite.de
First Name & Middle Initial & Last Name or Official Title & Degree
Julian Weingaertner, MD
Phone
030450657057
Email
julian.weingaertner@charite.de
Facility Information:
Facility Name
Klinik für Radioonkologie und Strahlentherapie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sebastian Zschaeck, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No

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Potential of Moderate Whole Body Hyperthermia to Enhance Response

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