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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Control group; Radiation: Hyperfractionated radiotherpy

• Study Type: Interventional
• Enrollment (Estimated): 308
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Maria Gebre-Medhin, MD; Phone Number: +46 46 17 75 20; Email: maria.gebre-medhin@skane.se
• Study Contact Backup: Name: Ingrid Müchler; Phone Number: +46 725 96 05 10; Email: Ingrid.Muchler@skane.se

Study Locations

• Sweden
  • Gävle, Sweden, SE-803 24
    • Not yet recruiting
    • Gävle Hospital
    • Contact: Ann-Sofie Fransson, MD; Phone Number: +46 26 15 40 00; Email: ann-sofie.fransson@regiongavleborg.se
    • Principal Investigator: Ann-Sofie Fransson, MD
  • Göteborg, Sweden, SE-413 46
    • Not yet recruiting
    • Sahlgrenska University Hospital
    • Contact: Hedda Haugen, MD; Phone Number: +46 31 343 60 42; Email: hedda.haugen@oncology.gu.se
    • Principal Investigator: Hedda Haugen, MD
  • Jönköping, Sweden, SE-553 05
    • Not yet recruiting
    • Jönköping Hospital
    • Contact: Mattias Olin, MD; Phone Number: +46 10 24 25 942; Email: mattias.olin@rjl.se
    • Principal Investigator: Mattias Olin, MD
  • Karlstad, Sweden
    • Not yet recruiting
    • Karlstad Hospital
    • Contact: Björn Kullinger, MD
    • Principal Investigator: Björn Kullinger, MD
  • Linköping, Sweden
    • Not yet recruiting
    • Linkoping University Hospital
    • Principal Investigator: Jan Rzepecki, MD
    • Contact: Jan Rzepecki, MD
  • Lund, Sweden, SE-221 85
    • Recruiting
    • Lund University Hospital
    • Contact: Maria Gebre-Medhin, MD; Phone Number: +46 46 17 75 20; Email: maria.gebre-medhin@skane.se
    • Principal Investigator: Maria Gebre-Medhin, MD
  • Stockholm, Sweden, SE-171 64
    • Not yet recruiting
    • Karolinska University Hospital
    • Contact: Michael Gubanski, MD; Phone Number: +46 8 517 700 00; Email: michael.gubanski@sll.se
    • Principal Investigator: Michael Gubanski, MD
  • Umeå, Sweden, SE-907 37
    • Not yet recruiting
    • University Hospital
    • Contact: Björn Zackrisson, MD; Phone Number: +46 90 785 00 00; Email: bjorn.zackrisson@onkologi.umu.se
    • Principal Investigator: Björn Zackrisson, MD
  • Uppsala, Sweden, SE-753 09
    • Not yet recruiting
    • Uppsala Accademical Hospital
    • Contact: Zahra Taheri Kadkhoda, MD; Phone Number: +46 18 611 00 00; Email: zahra.taheri.kadkhoda@akademiska.se
    • Principal Investigator: Zahra Taheri Kadkhoda, MD
  • Västerås, Sweden
    • Not yet recruiting
    • Västmanlands Hospital Västerås
    • Principal Investigator: Zuzana Lovasova, MD
    • Contact: Zuzana Lovasova, MD
  • Örebro, Sweden, SE-703 82
    • Not yet recruiting
    • Orebro University Hospital
    • Principal Investigator: Erik Lundin, MD
    • Contact: Erik Lundin, MD; Phone Number: +46 19 602 10 00; Email: erik.lundin@regionorebrolan.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient must be at least 18 years old.
2. 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.

3. The primary tumour must fulfil the following high-risk criteria:

   1. For p16+ oropharyngeal cancer: Radiographic measurement of threeorthogonal diameters must render a tumour estimate of ≥30 cc.
   2. For all other subsites and for p16- oropharyngeal cancer: Radiographic measurement of three orthogonal diameters must render a tumour estimate of ≥20 cc.
4. 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.
5. WHO/ECOG performance status 0-2
6. 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:

1. Previous radiotherapy in the head and neck region.
2. 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
3. Two or more synchronous primary HNSCC at time of diagnosis
4. Nasopharyngeal cancer
5. Sinonasal cancer
6. Co-existing disease prejudicing survival (expected survival < three years).
7. Pregnancy or lactation
8. Psychiatric or addictive disorders or other medical conditions which in the view of the investigator might impair patient compliance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventionally fractioned (standard) group; This groups is treated with standard radiotherapy treatment: RT 2.0 Gy daily to final radiation dose 68.0 Gy or	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.; Other Names: standard treatment
Experimental: HFX-RT group; Treated with Hyperfractionated radiotherapy (HFX-RT): Gy twice daily (10 fractions/week) with final dose 83.0 Gy	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.; Other Names: HFX-RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local tumour control after treatment	Local tumour control after treatment with conventionally fractionated (standard) RT compared with hyperfractionated radiotherapy (HFX-RT)	Every three months for two years, then every 6 moths up to 5 years

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Investigators: Principal Investigator: Maria Gebre-Medhin, MD, Lund University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 4, 2024
• Primary Completion (Estimated): March 4, 2028
• Study Completion (Estimated): March 4, 2033

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: radiotherapy; HNSCC; Head and neck squamous cell carcinoma; Hyperfractionated radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: ARTSCAN VI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No