Moderate Whole Body Hyperthermia for Patients Undergoing Re-irradiation for Head and Neck Cancer -Influence on the Tumor Microenvironment (GKH-TMM)

Gemäßigte Ganzkörperhyperthermie Bei Patienten Mit Rezidivierten Plattenepithelkarzinomen Der Kopf-Hals Region Nach Hochdosierter Vorbestrahlung: Pilotstudie Zur Beeinflussung Des Tumormikromilieus.

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms; Recurrence Tumor
• Intervention / Treatment: Device: Moderate whole body hyperthermia using water-filtered IR-A-radiation

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Klinik für Radioonkologie und Strahlentherapie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Additional application of weekly moderate whole-body hyperthermia concurrent to re-irradiation plus chemotherapy	Device: Moderate whole body hyperthermia using water-filtered IR-A-radiation; 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; Other Names: hypoxia imaging using 18f-fluoromisonidazole before radiochemotherapy and during second week of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	within 6 weeks of treatment with radiochemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year (recruitment) plus additional 2 weeks (evaluation of PET parameter)
magnetic resonance imaging (MRI) measured perfusion changes	measured before treatment and at the end of week 2	1 year (recruitment) plus additional 2 weeks (evaluation of MRI parameter)
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.	3 years (i.e. recruitment plus two years of follow-up)
Patient reported quality of life (general quality of life)	measured by questionnaires according to EORTC (C30) and Transformation of absolute values to percentual values.	3 years (i.e. recruitment plus two years of follow-up)
Local control after 2 years of follow-up	From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.	3 years (1 year recruitment, 2 years follow-up)
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.	3 years (1 year recruitment, 2 years follow-up)
Overall survival after 2 years of follow-up	From start of re-irradiation. Analysis will be performed by cox regression and log-rank analyses.	3 years (1 year recruitment, 2 years follow-up)
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.	3 years (1 year recruitment, 2 years follow-up)
Tumor response	Response of the irradiated tumor 3 months after end of treatment according to recist criteria	1 year (recruitment) and 3 months (follow-up)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Erwin Braun foundation
• Investigators: Principal Investigator: Sebastian Zschaeck, MD, Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): May 4, 2020
• Study Completion (Actual): May 4, 2020

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 5, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: PET; whole body hyperthermia; hyperthermia; positron emission tomography; hypoxia; head and neck squamous cell carcinoma; radiochemotherapy; local recurrence; FMISO; 18f-fluoromisonidazole; lymph node recurrence
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Wounds and Injuries; Disease Attributes; Body Temperature Changes; Heat Stress Disorders; Head and Neck Neoplasms; Recurrence; Hyperthermia
• Other Study ID Numbers: EA2/047/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: pseudonymized data may be shared upon reasonable request if accepted by all participating ethical commissions

Drug and device information, study documents

• 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