Clinical trial NCT05348486: FMISO-based Adaptive Radiotherapy for Head and Neck Cancer
Official title: FMISO-based Adaptive Radiotherapy for Head and Neck Cancer - a Prospective Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Head and Neck Cancer
Hypoxia
FMISO
Dose Escalation
Keywords: Head and Neck Cancer
Hypoxia
Radiotherapy
Dose escalation
Lead sponsor: University Hospital Olomouc
Sponsor class: OTHER
Collaborators: name: Masaryk Memorial Cancer Institute
name: University Hospital Ostrava
First posted: 2022-04-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypoxia occurs in about 80% of head and neck tumors. Based on experimental and clinical data, hypoxia is a useful parameter for pretherapeutic stratification. These radioresistant regions can be detected with FMISO PET/CT. Moreover, hypoxic subvolumes of tumors can be evolving as target volumes for radiotherapy ("dose painting") in hypoxia imaging-based dose escalation.

Detailed description: The radiotherapy protocol will include two dose-escalation regimens. The dose in hypoxic tumor volume will be escalated either by conventional RT or stereotactic radiotherapy technique. Concurrent chemotherapy cisplatin will be administered weekly 35-40 mg/m2 or every three weeks 80-100 mg/m2. The parameter of cumulative cisplatin dose of 200 mg/m2 during the whole course of radiotherapy will be also taken into account. Patients will be examined and monitored at least every two weeks.

Target volumes and dose and fractionation:

Definition of gross tumor volumes (GTV), clinical target volumes (CTV) and planning target volumes (PTV) will follow recommendations of DAHANCA, EORTC and RTOG guidelines.

The conventional radiotherapy protocol:

Standard fractionation regimen: 70 Gy/54 Gy in 33 fractions GTV primary - CTV - PTV (5+5mm): for dose 70 Gy in 33 fractions GTV LN bulky (\> 3cm) - PTV (5mm): for dose 70 Gy in 33 fractions LN low risk (for elective irradiation) - CTV - PTV (3mm-5mm): for dose 54 Gy in 33 fractions

Dose escalated radiotherapy protocol:

Dose escalated radiotherapy protocol: 75,9 - 79,2 Gy in 33 fractions GTV hypoxic or any hypoxic LN \> 2cm - PTV (0mm): dose 75,9 - 79,2 Gy in 33 fractions (Contours must be subtracted and reduce by 3mm in case of close relation to the skin, bones or large blood vessels) GTV primary - CTV - PTV (5+5mm): for dose 70 Gy in 33 fractions LN low risk (for elective irradiation) - CTV - PTV (3mm-5mm): for dose 54 Gy in 33 fractions

Eligibility criteria: Inclusion Criteria:

* Pathologically proven new diagnosis of oropharyngeal p16 negative, or laryngeal, hypopharyngeal, oral cavity (independent of p16) squamous cell carcinoma of clinical stage III, IV confined to head and neck area
* Evaluable tumor burden assessed by computed tomography scan or magnetic resonance imaging, based on RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1
* Eligibiity for definitive chemoradiation or hyperfractionated accelerated radiotherapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate kidney and liver function

Exclusion Criteria:

* Prior surgical treatment - any surgery of primary tumor or involved nodes or prior surgical debulking apart from surgery with diagnostic intention (e.g. open biopsy if necessary)
* Prior systemic therapy, targeted therapy, radiotherapy treatment for head and neck cancer
* Cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or unknown primary head and neck cancer
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis or any distant metastasis
* Known active Hepatitis B or C
* History of Human Immunodeficiency Virus (HIV)
* History of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
* Previous allogeneic tissue/solid organ transplant
* Active infection requiring systemic therapy

Primary outcomes:
measure: Complete response rate
timeFrame: 2-year
measure: Locoregional progresion free survival
timeFrame: 2-year
measure: Rate of acute (<3 months) radiation-induced events according to CTCAE 5.0
timeFrame: 3 months
measure: Rate of late radiation-induced events according to CTCAE 5.0
timeFrame: 2-year
Secondary outcomes:
measure: Overall survival
timeFrame: 4 years
measure: Distant metastasis free survival
timeFrame: 4 years
measure: Change in QoL according to the standardised EQ-5D questionnaire
timeFrame: 2 years
measure: Rate of new hypoxic areas after two weeks of radiotherapy
timeFrame: 2 week after start of radiotherapy
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: The Masaryk Memorial Cancer Institute
city: Olomouc
country: Czechia
facility: Radiation oncology department in Palacký University and University Hospital Olomouc
city: Ostrava
country: Czechia
facility: Faculty Hospital Ostrava
Study officials:
affiliation: Palacký University and University Hospital Olomouc
name: Martin Dolezel, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Masaryk Memorial Cancer Institute (MMCI)
name: Marek Slavik, Ph.D.
role: STUDY_CHAIR
affiliation: Faculty Hospital Ostrava
name: Jakub Cvek, Prof.
role: STUDY_CHAIR
References: