Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Interventions
- Radiation: dose-escalated radiochemotherapyRadiation: standard radiochemotherapyRadiation: dose-escalated radiochemotherapy with carbon ion boost
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 276
- 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)
- 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
- Arm && Interventions
Group Intervention Description dose-escalated radiochemotherapy, hypoxic dose-escalated radiochemotherapy HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to escalated radiation dose, 77 Gy radiochemotherapy standard radiochemotherapy, hypoxic standard radiochemotherapy HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy standard radiochemotherapy (70 Gy) standard radiochemotherapy HPV (+), HPV positive patients will get the same imaging and clinical examinations as HPV negative patients. This measure is necessary to further elucidate the prognostic role of hypoxia and HPV status and their correlation, the information will be important for consecutive clinical trials. 70 Gy standard radiochemotherapy. escalated radiochemoth., carbon boost, hypoxic dose-escalated radiochemotherapy with carbon ion boost HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, non-randomised arm (only possible in the trial center Heidelberg), 77 Gy radiochemotherapy (boost with carbon) standard radiochemotherapy, oxic standard radiochemotherapy HPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy
- 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)
Uniklinikum Wuerzburg
🇩🇪Würzburg, Bavaria, Germany
Mechthild Krause
🇩🇪Dresden, Saxony, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Saxony, Germany
Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie
🇩🇪Mannheim, Baden-Wuerttemberg, Germany
Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology
🇩🇪Freiburg, Baden-Wuerttemberg, Germany
Charité University Hospital
🇩🇪Berlin, Germany
Department of Radiation Oncology Heidelberg University Medical School
🇩🇪Heidelberg, Baden-Wuerttemberg, Germany
Ludwig-Maximilian-Universität, Klinikum Großhadern
🇩🇪München, Germany