Head and Neck CancerPhase 1PIRATESNCT06446713
PIRATES: Image-guided Hyper-fractioned Dose-escalation With Proton Therapy for Head and Neck Cancer
A Phase 1 study testing Image guided hybrid hyper-fractioned dose escalation with proton therapy in people with Head and Neck Cancer and Oropharyngeal Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Oropharyngeal Cancer
- What is being tested?
- Image guided hybrid hyper-fractioned dose escalation with proton therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 May 2025to 1 Jan 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
UMC Groningen
Groningen
L.V. van Dijk, dr., 031655257381, l.v.van.dijk@umcg.nl
About this study
Official title: Proton Image-guided Radiation Assignment for Therapeutic Escalation Via Selection of Locally Advanced Head and Neck Cancer Patients
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
Read the 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
- Being tested
- Image guided hybrid hyper-fractioned dose escalation with proton therapy
- Keywords
- Proton therapy, Hyperfractionation, Dose-escalation, Image guidance therapy, Adaptive radiotherapy
- Medical subject headings
- Head and Neck Neoplasms, Oropharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Image guided hybrid hyper-fractioned dose escalation with proton therapy | Experimental | Not described Receives: Radiation: Image guided hybrid hyper-fractioned dose escalation with proton therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 6 months after radiotherapy
Secondary outcomes (5)
Completing radiotherapy regimen
Completion of treatment with a maximum of 2 fraction interruption
Measured: End of radiotherapy
Completing chemotherapy regimen
Percentage of patients completing the complete chemotherapy regimen
Measured: 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).
Measured: At 6 months after chemoradiation
Tumor response rate
Preliminary tumor response rates measured on the standard follow-up MRI scan
Measured: 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
Measured: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start1 May 2025 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm Bayesian Phase I intervention study
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06446713
- Sponsor's protocol ID
- 18646
- Acronym
- PIRATES
- Status last verified
- Mar 2025
- First submitted
- 31 May 2024
- Last updated
- 3 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proton Image-guided Radiation Assignment for Therapeutic Escalation Via Selection of Locally Advanced Head and Neck Cancer Patients
- ClinicalTrials.gov ID
- NCT06446713
- Acronym / sponsor ID
- PIRATES / 18646
- Conditions
- Head and Neck Cancer, Oropharyngeal Cancer
- Keywords
- Proton therapy, Hyperfractionation, Dose-escalation, Image guidance therapy, Adaptive radiotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Study start
- 1 May 2025 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 6 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm Bayesian Phase I intervention study
| Arm | Type | Receives |
|---|---|---|
| Image guided hybrid hyper-fractioned dose escalation with proton therapy | Experimental | Radiation: Image guided hybrid hyper-fractioned dose escalation with proton therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Image guided hybrid hyper-fractioned dose escalation with proton therapyRadiation: 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. | Radiation | Image guided hybrid hyper-fractioned dose escalation with proton therapy |
Primary outcome
Safety and feasibility
Time frame: Within 6 months after radiotherapy
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
5 secondary outcomes
Completing radiotherapy regimen
Time frame: End of radiotherapy
Completing chemotherapy regimen
Time frame: End of chemotherapy
Toxicity after chemoradiation
Time frame: At 6 months after chemoradiation
Tumor response rate
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
Time frame: All SFP time points (baseline, weekly during RT, 6 weeks, 6, 12, 18, 24 months after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Image guided hybrid hyper-fractioned dose escalation with proton therapy in people with Head and Neck Cancer and Oropharyngeal Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and feasibility (time frame: Within 6 months after radiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.