Clinical trial NCT04607694: DAHANCA 35: Proton Versus Photon Therapy for Head-neck Cancer
Official title: DAHANCA 35: A Randomized Trial of Proton Versus Photon Radiotherapy for the Treatment of Head-neck Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Head-and-neck Cancer
Keywords: Proton radiotherapy
DAHANCA
Lead sponsor: Danish Head and Neck Cancer Group
Sponsor class: NETWORK
Collaborators: name: The Novo Nordic Foundation
First posted: 2020-10-29
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized clinical trial
Primary purpose: TREATMENT

Brief summary: Patients with squamous cell carcinoma of the pharynx or larynx and an anticipated benefit of proton radiotherapy in reducing the risk of late dysphagia or xerostomia are randomized to proton or photon radiotherapy (2:1)

Detailed description: DAHANCA 35 is two parallel conducted, but separate randomized studies, within the same trial (DAHANCA 35D and DAHANCA 35X) by the Danish Head-Neck Cancer Study Group (DAHANCA). In patients with squamous cell carcinoma of the pharynx or larynx planned for primary radiotherapy a proton and a photon doseplan is prepared. If proton radiotherapy reduces the anticipated absolute risk of dysphagia \>= grade 2 (DAHANCA scale, DAHANCA 35D) or severe xerostomia \>= grade 4 (EORTC Head-Neck 35, DAHANCA 35X) more than 5%, the patient is randomised to either proton therapy or photon therapy, 2:1. The anticipated risk of xerostomia and dysphagia is estimated using Normal-Tissue Complication Models (NTCP). Patient are analysed according to the primary endpoint (dysphagia and/or xerostomia) after which they were enrolled. DAHANCA 35D is expected to enroll 360 patients and DAHANCA 35X 240 patients (in total 600 patients).

Eligibility criteria: Inclusion Criteria:

* Patients with histologically proven squamous cell carcinoma of the pharynx or larynx planned for primary radiotherapy with curative intent
* A predicted clinical significant reduction in the risk of any of the two primary endpoints (\>= grade 2 observer-rated dysphagia or grade 4 patient-reported xerostomia) after proton therapy compared to photon therapy based on comparison of the individual patient dose plans
* No current or earlier malignancies, which may influence treatment, evaluation or outcome of the head-neck cancer
* Informed consent as required by law
* Above 18 years of age

Exclusion Criteria:

* Patient with cancers of the glottic larynx (stage I/II), skull base, sino-nasal area, unknown primary tumor and prior malignancies.
* Patients with contraindications for proton therapy. Per October 2020, this includes pacemakers, implanted defibrillators and tracheostomy
* Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic
* Distant metastasis
* Previous radiotherapy of the head and neck
* Previous surgery for the primary cancer with curative intent

Primary outcomes:
measure: Dysphagia >= grade 2
timeFrame: Six months after end of radiotherapy
measure: Xerostomia = grade 4
timeFrame: Six months after end of radiotherapy
Secondary outcomes:
measure: Loco-regional tumor control
timeFrame: Up to five years after end of radiotherapy
measure: Overall survival
timeFrame: Up to five years after end of radiotherapy
measure: Number of participants with disease-free survival
timeFrame: Up to five years after end of radiotherapy
measure: Disease-specific survival
timeFrame: Up to five years after end of radiotherapy
measure: Acute toxicity
timeFrame: From the beginning of and up to two months after end of radiotherapy
measure: Late toxicity
timeFrame: From two months to five years after end of radiotherapy
measure: EORTC QLQ-Head-Neck 35
timeFrame: Up to ten years after end of radiotherapy
measure: EORTC C30
timeFrame: Up to ten years after end of radiotherapy
measure: MD Anderson Dysphagia Index
timeFrame: Up to ten years after end of radiotherapy
measure: EuroQol Five Dimension Scale (EQ-5D)
timeFrame: Up to ten years after end of radiotherapy
measure: Composite time corrected toxicity score (CTCT)
timeFrame: Up to five years after end of radiotherapy
measure: Modified barium swallowing
timeFrame: One year after end of radiotherapy
measure: Stimulated whole-mouth salivary flow
timeFrame: Up to five years after end of radiotherapy
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Aarhus
country: Denmark
facility: Danish Center for Particle Therapy
city: Copenhagen
country: Denmark
facility: Herlev Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Næstved
country: Denmark
facility: Næstved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Danish Head-Neck Cancer Group (DAHANCA)
name: Jeppe Friborg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: