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

NCT06446713 | Recruiting Phase 1 DMC

• 1 other identifier: 18646
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Conditions

Head and Neck Cancer; Oropharyngeal Cancer

Keywords

Proton therapy; Hyperfractionation; Dose-escalation; Image guidance therapy; Adaptive radiotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  Within 6 months after radiotherapy

Secondary Outcomes (5)

• Completing radiotherapy regimen

  End of radiotherapy

• Completing chemotherapy regimen

  End of chemotherapy

• Toxicity after chemoradiation

  At 6 months after chemoradiation

• Tumor response rate

  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

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

Other Outcomes (4)

• Other physician rated toxicities

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

• Patient-rated symptoms

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

• Quality of life

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

Study Arms (1)

Image guided hybrid hyper-fractioned dose escalation with proton therapy

EXPERIMENTAL

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

Interventions

Image guided hybrid hyper-fractioned dose escalation with proton therapy 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.

Image guided hybrid hyper-fractioned dose escalation with proton therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

UMC Groningen

Groningen, Netherlands

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Oropharyngeal Neoplasms

Interventions

Proton Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: All participants receive the experimental treatment
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm Bayesian Phase I intervention study

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 6, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 3, 2025

Record last verified: 2025-03

Locations

NL (1)