a Multicentre Phase III Study of Risk-based Treatment Intensification With Hyperfractionated Radiotherapy in Head and Neck Cancer Patients

Official title

ARTSCAN VI Protocol Version 1, 2023-07-03 ARTSCAN VI - a Multicentre Phase III Study of Risk-based Treatment Intensification With Hyperfractionated Radiotherapy in Head and Neck Cancer Patients

Overview

There is an unmet need to personalise treatment for patients with head and neck squamous cell carcinoma (HNSCC) and to improve treatment results for patients with advanced disease. In this phase III study, HNSCC patients with prognostic factors indicating increased risk of treatment failure that are aimed for curative treatment with radiotherapy (RT) will be randomised between standard treatment (conventionally fractionated RT with final RT dose 68.0 Gy) and hyperfractionated RT (HFX-RT) with final RT dose 83.0 Gy. In order to find better prognostic and predictive tools the study also includes exploratory and translational analyses including evaluation of grade of hypoxia with Magnetic Resonance Imaging (MRI) and gene profiling by RNA-sequencing, tumour immune profiling, comparisons of global gene expression, gene aberrations and protein expression, and texture analyses of CT, FDG-PET and MRI images used during RT preparation and during patient follow-up. Patients with tumours with lower risk of recurrence, not eligible for randomisation in the study, can still participate in the translational parts of the study not investigating response to altered fractionation.

Interventions

• Radiation Hyperfractionated radiotherpy
  83.0 Gy in 68 fractions, 1.22 Gy per fraction, two daily fractions, five days per week to the primary tumour volume (GTVT\_83.0). To the primary tumour with an added margin (PTVT\_74.8) and to neck node metastases (PTVN\_74.8) the prescribed dose will be 74.8 Gy in 68 fractions, 1.10 Gy per fraction twice daily. To elective neck nodes (PTV 54.4) the prescribed dose will be 54.4 Gy in 68 fractions, 0.80 Gy per fraction twice daily.
• Radiation Control group
  68.0 Gy in 34 fractions, 2.00 Gy per fraction per day, five or six days per week to tumour volumes and 54.4 Gy in 34 fractions, 1.60 Gy per fraction to elective neck nodes.

Primary outcome measures

• Local tumour control after treatment [Time frame: Every three months for two years, then every 6 moths up to 5 years]

Eligibility criteria

Inclusion criteria

• The patient must be at least 18 years old.
• Histologically or cytologically confirmed, previously untreated, HNSCC of the oropharynx, hypopharynx, larynx or oral cavity without distant metastases and aimed for treatment with radiotherapy (with or without concomitant chemotherapy) with curative intent.
• The primary tumour must fulfil the following high-risk criteria:

• For p16+ oropharyngeal cancer: Radiographic measurement of threeorthogonal diameters must render a tumour estimate of ≥30 cc.
• For all other subsites and for p16- oropharyngeal cancer: Radiographic measurement of three orthogonal diameters must render a tumour estimate of ≥20 cc.
• The treatment may be followed but not preceded by surgery, either as a salvage procedure or a neck dissection. An excision of a lymph node or tonsillectomy for diagnostic purposes, does not exclude the patient from participation.
• WHO/ECOG performance status 0-2
• The patient must be able to understand the information about the treatment and give a written informed consent to participate in the trial.

Exclusion criteria

• Previous radiotherapy in the head and neck region.
• Concomitant or previous malignancies, except uncomplicated basal cell carcinoma, early (T1-2 N0) squamous cell carcinoma of the skin with follow-up time of at least one year for squamous cell carcinomas, and except other cancer with a disease-free follow-up of at least three years
• Two or more synchronous primary HNSCC at time of diagnosis
• Nasopharyngeal cancer
• Sinonasal cancer
• Co-existing disease prejudicing survival (expected survival < three years).
• Pregnancy or lactation
• Psychiatric or addictive disorders or other medical conditions which in the view of the investigator might impair patient compliance

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 11 centers

• Gävle Hospital — Gävle
• Sahlgrenska University Hospital — Gothenburg
• Jönköping Hospital — Jönköping
• Karlstad Hospital — Karlstad
• Linköping University hospital — Linköping
• Lund University Hospital — Lund
• Örebro University Hospital — Örebro
• Karolinska University Hospital — Stockholm
• … and 3 more centers

Identifiers

NCT: NCT06248996 · ARTSCAN VI

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗