FMISO-based Adaptive Radiotherapy for Head and Neck Cancer (FARHEAD)

FMISO-based Adaptive Radiotherapy for Head and Neck Cancer - a Prospective Multicenter Study

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.

Study Overview

• Status: Recruiting
• Conditions: Hypoxia; Head and Neck Cancer; Dose Escalation; FMISO
• Intervention / Treatment: Radiation: 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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Dolezel, Prof; Phone Number: +420588444295; Email: dolezelm@email.cz

Study Locations

• Czechia
  • Brno, Czechia
    • Recruiting
    • The Masaryk Memorial Cancer Institute
    • Contact: Marek Slavik, Ph.d.
  • Olomouc, Czechia
    • Recruiting
    • Radiation oncology department in Palacký University and University Hospital Olomouc
    • Contact: Martin Dolezel, Prof; Phone Number: +420588444295; Email: dolezelm@email.cz
  • Ostrava, Czechia
    • Recruiting
    • Faculty Hospital Ostrava
    • Contact: Jakub Cvek, Ass.Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Radiation: Dose escalation; Dose escalation 75,9 - 79,2 Gy in 33 fractions for GTV hypoxic or any hypoxic LN > 2cm
No Intervention: Standard fractionation; Standard fractionation regimen: 70 Gy/54 Gy in 33 fractions GTV primary - CTV - PTV (5+5mm): for dose 70 Gy/33 GTV LN bulky (> 3cm) - PTV (5mm): for dose 70 Gy/33 LN low risk (for elective irradiation) - CTV - PTV (3mm-5mm): for dose 54 Gy/33

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital Olomouc
• Collaborators: University Hospital Ostrava; Masaryk Memorial Cancer Institute
• Investigators: Principal Investigator: Martin Dolezel, Prof., Palacký University and University Hospital Olomouc; Study Chair: Marek Slavik, Ph.D., The Masaryk Memorial Cancer Institute (MMCI); Study Chair: Jakub Cvek, Prof., Faculty Hospital Ostrava

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Hypoxia; Radiotherapy; Dose escalation
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Signs and Symptoms, Respiratory; Hypoxia; Head and Neck Neoplasms
• Other Study ID Numbers: 22-03-00435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No