Back to resultsModerate Whole Body Hyperthermia for Patients Undergoing Re-irradiation for Head and Neck Cancer -Influence on the Tumor Microenvironment (GKH-TMM)
Primary Purpose
Head and Neck Neoplasms, Recurrence Tumor
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Moderate whole body hyperthermia using water-filtered IR-A-radiation
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Neoplasms focused on measuring head and neck squamous cell carcinoma, hyperthermia, hypoxia, 18f-fluoromisonidazole, positron emission tomography, FMISO, PET, whole body hyperthermia, local recurrence, lymph node recurrence, radiochemotherapy
Eligibility Criteria
Inclusion Criteria:
- patients with unresectable local, regional or loco-regional recurrent non HPV-associated squamous cell head and neck cancer with prior high-dose radiotherapy of the head and neck region
- time interval of 6 months to 5 years after completion of last radiotherapy of the head and neck region
- Completed staging examinations, preferentially 18f-fluorodeoxyglucose (FDG) PET of the whole body
- general health condition according to ECOG status of 0,1 or 2
- age between 18 and 75 years
- written informed consent
Exclusion Criteria:
- HPV associated primary tumor or recurrent tumor
- recurrence more than 5 years after end of previous radiotherapy
- Any medical circumstances impeding the application of radiotherapy, concomitant chemotherapy or whole body hyperthermia
Sites / Locations
- Klinik für Radioonkologie und Strahlentherapie
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
Additional application of weekly moderate whole-body hyperthermia concurrent to re-irradiation plus chemotherapy
Outcomes
Primary Outcome Measures
feasibility of whole body hyperthermia as adjunct to radiochemotherapy
feasibility is defined as at least 4 cycles of whole body hyperthermia in 80% of patients
Secondary Outcome Measures
Reduction of positron emission tomography (PET) measured hypoxia
defined as at least 80% reduction of the tumor to background ratio measured at the end of the second week of treatment compared to pre-treatment
magnetic resonance imaging (MRI) measured perfusion changes
measured before treatment and at the end of week 2
Patient reported quality of life (head and neck cancer specific quality of life)
measured by questionnaires according to EORTC (H&N35) and Transformation of absolute values to percentual values.
Patient reported quality of life (general quality of life)
measured by questionnaires according to EORTC (C30) and Transformation of absolute values to percentual values.
Local control after 2 years of follow-up
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Loco-regional control after 2 years of follow-up
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Overall survival after 2 years of follow-up
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Freedom from distant metastases after 2 years of follow-up
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Tumor response
Response of the irradiated tumor 3 months after end of treatment according to recist criteria
Full Information
NCT ID
NCT03547388
First Posted
March 27, 2018
Last Updated
May 4, 2020
Sponsor
Charite University, Berlin, Germany
Collaborators
Erwin Braun foundation
1. Study Identification
Unique Protocol Identification Number
NCT03547388
Brief Title
Moderate Whole Body Hyperthermia for Patients Undergoing Re-irradiation for Head and Neck Cancer -Influence on the Tumor Microenvironment
Acronym
GKH-TMM
Official Title
Gemäßigte Ganzkörperhyperthermie Bei Patienten Mit Rezidivierten Plattenepithelkarzinomen Der Kopf-Hals Region Nach Hochdosierter Vorbestrahlung: Pilotstudie Zur Beeinflussung Des Tumormikromilieus.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
May 4, 2020 (Actual)
Study Completion Date
May 4, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
Erwin Braun foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of the study is to determine the feasibility and efficacy of moderate weekly whole Body hyperthermia Treatment during radiochemotherapy for pre-irradiated locally or regionally recurrent head and neck squamous cell carcinomas.
The Primary aim of the study is feasibility, defined as 80% of patients completing at least four applications of hyperthermia.
Secondary endpoints include an increase of Tumor Perfusion by the use of hyperthermia, measured by magnetic resonance Imaging during week two of Treatment and reduction of Tumor hypoxia, measured by hypoxia specific Positron emission tomography.
Detailed Description
Previously irradiated patients with loco/ loco-regional recurrent head and neck squamous cell carcinomas usually undergo re-irradiation. However prognosis of these patients is unfavourable, especially for non-human papilloma virus associated cancers. Moderate whole body hyperthermia will be performed by water-filtered IR-A-radiation using a Heckel-HT3000 device.
Preclinical data have indicated that moderate whole body hyperthermia decreases intratumoral interstitial fluid pressure and leads to increased perfusion of the tumor. The study investigates if this holds also true in patients and leads to a marked decrease of tumor hypoxia, measured by 18F-Fluoromisonidazole PET.
The Primary aim of the study is feasibility, defined as 80% of patients completing at least four applications of hyperthermia.
Secondary endpoints include an increase of Tumor Perfusion by the use of hyperthermia, measured by magnetic resonance Imaging during week two of Treatment and reduction of Tumor hypoxia, measured by hypoxia specific Positron emission tomography.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Neoplasms, Recurrence Tumor
Keywords
head and neck squamous cell carcinoma, hyperthermia, hypoxia, 18f-fluoromisonidazole, positron emission tomography, FMISO, PET, whole body hyperthermia, local recurrence, lymph node recurrence, radiochemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase I feasibility study
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Arm Description
Additional application of weekly moderate whole-body hyperthermia concurrent to re-irradiation plus chemotherapy
Intervention Type
Device
Intervention Name(s)
Moderate whole body hyperthermia using water-filtered IR-A-radiation
Other Intervention Name(s)
hypoxia imaging using 18f-fluoromisonidazole before radiochemotherapy and during second week of treatment
Intervention Description
four to six applications of whole Body hyperthermia concomitant to radiochemotherapy. Additional measurement of Perfusion and hypoxia by 18F-FMISO hypoxia PET and magnetic resonance Imaging
Primary Outcome Measure Information:
Title
feasibility of whole body hyperthermia as adjunct to radiochemotherapy
Description
feasibility is defined as at least 4 cycles of whole body hyperthermia in 80% of patients
Time Frame
within 6 weeks of treatment with radiochemotherapy
Secondary Outcome Measure Information:
Title
Reduction of positron emission tomography (PET) measured hypoxia
Description
defined as at least 80% reduction of the tumor to background ratio measured at the end of the second week of treatment compared to pre-treatment
Time Frame
1 year (recruitment) plus additional 2 weeks (evaluation of PET parameter)
Title
magnetic resonance imaging (MRI) measured perfusion changes
Description
measured before treatment and at the end of week 2
Time Frame
1 year (recruitment) plus additional 2 weeks (evaluation of MRI parameter)
Title
Patient reported quality of life (head and neck cancer specific quality of life)
Description
measured by questionnaires according to EORTC (H&N35) and Transformation of absolute values to percentual values.
Time Frame
3 years (i.e. recruitment plus two years of follow-up)
Title
Patient reported quality of life (general quality of life)
Description
measured by questionnaires according to EORTC (C30) and Transformation of absolute values to percentual values.
Time Frame
3 years (i.e. recruitment plus two years of follow-up)
Title
Local control after 2 years of follow-up
Description
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Time Frame
3 years (1 year recruitment, 2 years follow-up)
Title
Loco-regional control after 2 years of follow-up
Description
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Time Frame
3 years (1 year recruitment, 2 years follow-up)
Title
Overall survival after 2 years of follow-up
Description
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Time Frame
3 years (1 year recruitment, 2 years follow-up)
Title
Freedom from distant metastases after 2 years of follow-up
Description
From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.
Time Frame
3 years (1 year recruitment, 2 years follow-up)
Title
Tumor response
Description
Response of the irradiated tumor 3 months after end of treatment according to recist criteria
Time Frame
1 year (recruitment) and 3 months (follow-up)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients with unresectable local, regional or loco-regional recurrent non HPV-associated squamous cell head and neck cancer with prior high-dose radiotherapy of the head and neck region
time interval of 6 months to 5 years after completion of last radiotherapy of the head and neck region
Completed staging examinations, preferentially 18f-fluorodeoxyglucose (FDG) PET of the whole body
general health condition according to ECOG status of 0,1 or 2
age between 18 and 75 years
written informed consent
Exclusion Criteria:
HPV associated primary tumor or recurrent tumor
recurrence more than 5 years after end of previous radiotherapy
Any medical circumstances impeding the application of radiotherapy, concomitant chemotherapy or whole body hyperthermia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sebastian Zschaeck, MD
Organizational Affiliation
Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinik für Radioonkologie und Strahlentherapie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
pseudonymized data may be shared upon reasonable request if accepted by all participating ethical commissions
Citations:
PubMed Identifier
33626457
Citation
Zschaeck S, Weingartner J, Ghadjar P, Wust P, Mehrhof F, Kalinauskaite G, Ehrhardt VH, Hartmann V, Tinhofer I, Heiland M, Coordes A, Kofla G, Budach V, Stromberger C, Beck M. Fever range whole body hyperthermia for re-irradiation of head and neck squamous cell carcinomas: Final results of a prospective study. Oral Oncol. 2021 May;116:105240. doi: 10.1016/j.oraloncology.2021.105240. Epub 2021 Feb 21.
Results Reference
derived
Learn more about this trial
Moderate Whole Body Hyperthermia for Patients Undergoing Re-irradiation for Head and Neck Cancer -Influence on the Tumor Microenvironment
We'll reach out to this number within 24 hrs