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

Phase 1RecruitingNCT06446713

University Medical Center Groningen17 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Head and Neck Cancer Oropharyngeal Cancer

Interventions

Image guided hybrid hyper-fractioned dose escalation with proton therapyRADIATION

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

UMC Groningen

Groningen, Netherlands

RECRUITING

Outcomes

Primary Outcomes

Safety and feasibility

The number of dose limiting toxicity (DLT) events, defined as grade ≥4 mucositis, grade ≥4 ulceration, grade ≥4 dermatitis, grade ≥4 aspiration, grade ≥4 osteonecrosis and grade ≥3 myelopathy

Time frame: Within 6 months after radiotherapy

Secondary Outcomes

Completing radiotherapy regimen

Completion of treatment with a maximum of 2 fraction interruption

Time frame: End of radiotherapy

Completing chemotherapy regimen

Percentage of patients completing the complete chemotherapy regimen

Time frame: End of chemotherapy

Toxicity after chemoradiation

Rates of grade ≥3 mucositis, dermatitis, aspiration, dysphagia, hearing impaired, xerostomia, weight loss, trismus, hoarseness, oropharyngeal pain (according to CTCAEv5).

Time frame: At 6 months after chemoradiation

Tumor response rate

Preliminary tumor response rates measured on the standard follow-up MRI scan

Time frame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment

Disease-free, overall survival and time-weighted locoregional control

Preliminary disease-free, overall survival and time-weighted locoregional control analyses

Time frame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment

Data from ClinicalTrials.gov

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