FMISO-based Adaptive Radiotherapy for Head and Neck Cancer

Not Applicable

Recruiting

• Conditions: Head and Neck Cancer; Hypoxia; FMISO; Dose Escalation
• Interventions: Radiation: Dose escalation

• Registration Number: NCT05348486
• Lead Sponsor: University Hospital Olomouc

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

Study Timeline

• Study Start: 2022-04-20
• Study First Submitted: 2022-04-20
• Study First Submitted QC: 2022-04-20
• Study First Posted: 2022-04-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-16
• Last Update Posted: 2025-04-22
• Primary Completion: 2025-06-30
• Study Completion: 2030-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose escalation	Dose escalation	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/33 (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/33 LN low risk (for elective irradiation) - CTV - PTV (3mm-5mm): for dose 54 Gy/33

Primary Outcome Measures

Name	Time	Method
Complete response rate	2-year	response rate
Rate of late radiation-induced events according to CTCAE 5.0	2-year	late radiation-induced events
Rate of acute (<3 months) radiation-induced events according to CTCAE 5.0	3 months	acute radiation-induced events
Locoregional progresion free survival	2-year	locoregional progresion free survival

Secondary Outcome Measures

Name	Time	Method
Distant metastasis free survival	4 years	distant metastasis free survival
Change in QoL according to the standardised EQ-5D questionnaire	2 years	QoL according to the standardised EQ-5D questionnaire
Rate of new hypoxic areas after two weeks of radiotherapy	2 week after start of radiotherapy	rate of new hypoxic areas after two weeks of radiotherapy
Overall survival	4 years	overall survival

Trial Locations

Locations (3)

Radiation oncology department in Palacký University and University Hospital Olomouc; 🇨🇿 Olomouc, Czechia

The Masaryk Memorial Cancer Institute; 🇨🇿 Brno, Czechia

Faculty Hospital Ostrava; 🇨🇿 Ostrava, Czechia