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

ConditionsHead and Neck Cancer Oropharyngeal Cancer

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity Medical Center Groningen

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Stage III-IV

Disqualifiers

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

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.

Trial design

Design model

Single group

Treatments tested in this trial

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.

Treatment groups

17 Participants

are divided into 1 treatment group

Group A: Image guided hybrid hyper-fractioned dose escalation with proton therapyExperimental treatment 1 intervention

Trial 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