Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging

Phase 2

Not yet recruiting

• Conditions: Head and Neck Squamous Cell Carcinoma

• Registration Number: NCT03865277
• Lead Sponsor: Technische Universität Dresden

Brief Summary

The trial evaluates the value of radiation dose escalation based on Hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy or radiochemotherapy with escalated radiation dose. An additional interventional arm includes a carbon ion boost. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy.

Detailed Description

Previous preclinical data and a prospective validated patient cohort have shown that patients with head and neck squamous cell carcinoma, whose tumours are hypoxic after 2 weeks of primary radiochmeotherapy, have a significantly lower chance of locoregional tumour control. The multi-center trial evaluates the value of radiation dose escalation based on hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy (70 Gy) or radiochemotherapy with escalated radiation dose (77 Gy). An additional interventional arm includes a carbon ion boost to 77 Gy. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy. Secondary endpoints include acute and late toxicity (CTCAE 5.0), regional tumor control, overall survival, disease free survival, distant metastases, kinetics analysis of dynamic FMISO-PET scans, Quality of life (QoL). The hypothesis is that local tumour control 2 years after radiochemotherapy is higher in the dose escalated compared to the control arm.

Study Timeline

• Study First Submitted: 2019-02-26
• Study First Submitted QC: 2019-03-05
• Study First Posted: 2019-03-06
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-08
• Last Update Posted: 2023-09-11
• Study Start: 2024-07-01
• Primary Completion: 2025-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 276

Inclusion Criteria

• Age: older than 18 years
• WHO (ECOG) performance status 0-2
• Histological proven HNSCC
• HPV negative tumors or HPV positive tumors
• Stage III, IVA or IVB HNSCC according to UICC and AJCC guidelines
• Tumor classified as irresectable or patient inoperable or patient refused surgery
• Tumor extension and localization suitable for radiochemotherapy with curative intent
• Simultaneous standard chemotherapy with cisplatin applicable (no contra-indications)
• Dental examination and -treatment before start of therapy
• For women with childbearing potential and men in reproductive ages adequate contraception.
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria

• Refusal of the patients to take part in the trial
• Presence of distant metastases (UICC stage IVC)
• Previous radiotherapy in the head and neck region
• Second malignancy that is likely to require treatment during the trial intervention or follow-up period or that, in the opinion of the physician, has a considerable risk of recurrence or metastases within the follow-up period
• Serious disease or medical condition with life expectancy of less than one year
• Participation in competing interventional trial on cancer treatment
• Patients who are not suitable for radiochemotherapy
• Pregnant or lactating women
• Patients not able to understand the character and individual consequences of the trial
• Nasopharyngeal Carcinomas

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
local tumour control	Local tumor control 2 years after end of treatment	Local tumour control (MRI, CT, PET or clinical evaluation) in the randomized dose-escalated arm compared to the randomized non dose escalated arm (arms 1 and 2).

Secondary Outcome Measures

Name	Time	Method
late toxicity	30 days to 2 years after radiochemotherapy	late toxicity based on CTCAE 5.0
survival	2 years after radiochemotherapy	Overall survival
quality of life EORTC QLQ-C30/HN-35	regularly up to 2 years after radiochemotherapy	EORTC-QLQ (C30 and HN-35) Sheets (General for tumour diseases and specific for head and neck cancer)
acute toxicity	during treatment and up to 30 days after radiochemotherapy	acute toxicity based on CTCAE 5.0

Trial Locations

Locations (8)

Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology; 🇩🇪 Freiburg, Baden-Wuerttemberg, Germany

Department of Radiation Oncology Heidelberg University Medical School; 🇩🇪 Heidelberg, Baden-Wuerttemberg, Germany

Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie; 🇩🇪 Mannheim, Baden-Wuerttemberg, Germany

Uniklinikum Wuerzburg; 🇩🇪 Würzburg, Bavaria, Germany

Mechthild Krause; 🇩🇪 Dresden, Saxony, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Saxony, Germany

Charité University Hospital; 🇩🇪 Berlin, Germany

Ludwig-Maximilian-Universität, Klinikum Großhadern; 🇩🇪 München, Germany