PIRATES: Image-guided Hyper-fractioned Dose-escalation With Proton Therapy for Head and Neck Cancer

NCT ID: NCT06446713

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2029-01-01

Brief Summary

In this study the safety & feasibility of image-guided mid-treatment hyper-fractioned dose-escalation with proton therapy will be assessed for the treatment of locally advanced HPV-negative squamous cell oropharyngeal cancer

Detailed Description

For this study, the investigators propose a novel design to safely achieve tumor radiation dose escalation with proton therapy plus standard-of-care concomitant chemotherapy. Through mid-treatment image guidance, the tumor boost dose is determined; subsequently, only that GTV boost will receive a total dose of 80 Gy through hybrid hyperfractionation. This refers to twice-daily radiation in the last 15 fraction days. The combination of boost dose hyperfractionation and proton therapy is anticipated to prevent critical normal tissue damage within both the high- and intermediate-dose regions. This novel treatment approach aims to minimize critical toxicities while improving locoregional control for head and neck cancer patients who are at a higher risk of disease relapse.

Conditions

Head and Neck Cancer; Oropharyngeal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Image guided hybrid hyper-fractioned dose escalation with proton therapy

Group Type: EXPERIMENTAL

Image guided hybrid hyper-fractioned dose escalation with proton therapy

Intervention Type: RADIATION

Radiation: Image-guided hybrid hyper-fractioned dose escalation with proton therapy

The investigational radiation regime will be administered in a two-part schedule:

• The first 4 weeks (i.e. first 20 fractions) of the radiation treatment of the pathological tumor will be according to the conventional clinical standard with proton therapy: 20x 2 Gy to the CTV70 and 20 x 1.55 Gy to the CTV54.
• In week 4 (~ fraction 16) GTV80 will be determined on conventional weekly CT and additional MR imaging (conventional clinical protocol). Only this adapted tumor volume, the so-called GTV80, will receive the dose escalation (i.e., 80.5 Gy).
• In the last 3 weeks (last 15 fractions) patients will be radiated twice per day (i.e. hyperfractionation). The GTV80, CTV70 and CTV54 will receive 1.55 Gy in the morning, and the GTV80 and CTV70 will receive additional dose in the afternoon.

Interventions

Image guided hybrid hyper-fractioned dose escalation with proton therapy

Radiation: Image-guided hybrid hyper-fractioned dose escalation with proton therapy

The investigational radiation regime will be administered in a two-part schedule:

• The first 4 weeks (i.e. first 20 fractions) of the radiation treatment of the pathological tumor will be according to the conventional clinical standard with proton therapy: 20x 2 Gy to the CTV70 and 20 x 1.55 Gy to the CTV54.
• In week 4 (~ fraction 16) GTV80 will be determined on conventional weekly CT and additional MR imaging (conventional clinical protocol). Only this adapted tumor volume, the so-called GTV80, will receive the dose escalation (i.e., 80.5 Gy).
• In the last 3 weeks (last 15 fractions) patients will be radiated twice per day (i.e. hyperfractionation). The GTV80, CTV70 and CTV54 will receive 1.55 Gy in the morning, and the GTV80 and CTV70 will receive additional dose in the afternoon.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Biopsy proven diagnosis of squamous cell carcinoma originating in the oropharynx.
• Routine staging procedures, including CT of the head and neck region and chest, head and neck FDG-PET/CT and MRI (treatment planning allowed), and endoscopic evaluation when indicated.
• Negative for p16
• Locally advanced disease, specifically meeting all following criteria:

• Stage III-IV
• T-stage 2-4
• All N-stages (N0-3)
• M0
• Eligible for primary concurrent chemoradiation using conventionally fractionated radiotherapy 70 Gy combined with weekly cisplatin
• Eastern Cooperative Oncology Group (ECOG) performance score ≥2
• Age ≥18 years
• Written informed consent

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study; patients that:

• underwent definitive resection of their primary tumor or nodal disease, except for incisional or excisional biopsies.

received radiation therapy in the head and neck area in the past

• have no detectable tumor anymore at both the primary site and lymph nodes at week 4 in treatment, because there will not be a volume to boost.
• are unable or unwilling to give written, informed consent
• have contra-indications for chemotherapy. This is at the discretion of the treating medical oncologist.
• are unable to tolerate intravenous contrast for both CT and MRI, having an estimated GFR < 60 ml/min/1.73 m2 or any contraindications to gadolinium-based contrast agents.
• have any evidence of iron overload on pre-imaging laboratory studies.
• have other serious illnesses or medical conditions present at entry in the study, including (but not limited to): immunodeficiency virus (HIV) infection or other conditions of persistent immunodeficiency, neurologic or psychiatric disorders, active disseminated intravascular coagulation, unstable cardiac disease despite treatment or uncontrolled diabetes mellitus.
• Women who are pregnant or breast feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UMC Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Facility Contacts

L.V. van Dijk, dr.

Role: primary

l.v.van.dijk@umcg.nl

031655257381

Other Identifiers

18646

Identifier Type: -

Identifier Source: org_study_id