Clinical trial NCT06446713: PIRATES: Image-guided Hyper-fractioned Dose-escalation With Proton Therapy for Head and Neck Cancer
Official title: Proton Image-guided Radiation Assignment for Therapeutic Escalation Via Selection of Locally Advanced Head and Neck Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Head and Neck Cancer
Oropharyngeal Cancer
Keywords: Proton therapy
Hyperfractionation
Dose-escalation
Image guidance therapy
Adaptive radiotherapy
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: M.D. Anderson Cancer Center
First posted: 2024-06-06
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm Bayesian Phase I intervention study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety and feasibility
timeFrame: Within 6 months after radiotherapy
Secondary outcomes:
measure: Completing radiotherapy regimen
timeFrame: End of radiotherapy
measure: Completing chemotherapy regimen
timeFrame: End of chemotherapy
measure: Toxicity after chemoradiation
timeFrame: At 6 months after chemoradiation
measure: Tumor response rate
timeFrame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
measure: Disease-free, overall survival and time-weighted locoregional control
timeFrame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
Other outcomes:
measure: Other physician rated toxicities
timeFrame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
measure: Patient-rated symptoms
timeFrame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
measure: Quality of life
timeFrame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
measure: WHO performance
timeFrame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
Locations:
city: Groningen
country: Netherlands
facility: UMC Groningen
Study officials:
References: