Clinical trial NCT03865277: Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging
Official title: Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging: Multi-center, Randomized Phase-II-trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Head and neck cancer
radiochemotherapy
HPV
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2019-03-06
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: local tumour control
timeFrame: Local tumor control 2 years after end of treatment
Secondary outcomes:
measure: late toxicity
timeFrame: 30 days to 2 years after radiochemotherapy
measure: survival
timeFrame: 2 years after radiochemotherapy
measure: quality of life EORTC QLQ-C30/HN-35
timeFrame: regularly up to 2 years after radiochemotherapy
measure: acute toxicity
timeFrame: during treatment and up to 30 days after radiochemotherapy
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology
state: Baden-Wuerttemberg
city: Heidelberg
country: Germany
facility: Department of Radiation Oncology Heidelberg University Medical School
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie
state: Baden-Wuerttemberg
city: Würzburg
country: Germany
facility: Uniklinikum Wuerzburg
state: Bavaria
city: Dresden
country: Germany
facility: Mechthild Krause
state: Saxony
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Saxony
city: Berlin
country: Germany
facility: Charité University Hospital
city: München
country: Germany
facility: Ludwig-Maximilian-Universität, Klinikum Großhadern
Study officials:
affiliation: University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
name: Mechthild Krause, Prof.
role: STUDY_CHAIR
References: