DAHANCA 35: Proton Versus Photon Therapy for Head-neck Cancer

Not Applicable

Recruiting

• Conditions: Head-and-neck Cancer
• Interventions: Radiation: Proton radiotherapy; Radiation: Photon radiotherapy

• Registration Number: NCT04607694
• Lead Sponsor: Danish Head and Neck Cancer Group

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).

Study Timeline

• Status Verified: 2020-10
• Study Start: 2020-10-09
• Study First Submitted: 2020-10-19
• Study First Submitted QC: 2020-10-23
• Last Update Submitted: 2020-10-23
• Study First Posted: 2020-10-29
• Last Update Posted: 2020-10-29
• Primary Completion: 2025-03
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Proton radiotherapy	Proton radiotherapy	Proton radiotherapy according to the guidelines defined by the Danish Head-Neck Cancer Group (DAHANCA). Treatment: 66-68 Gy/ 33-34 fx/ 6/W, with cisplatin 40 mg/m2/W and nimorazole to suitable patients
Photon radiotherapy	Photon radiotherapy	Photon radiotherapy according to the guidelines defined by the Danish Head-Neck Cancer Group (DAHANCA). Treatment: 66-68 Gy/ 33-34 fx/ 6/W, with cisplatin 40 mg/m2/W and nimorazole to suitable patients

Primary Outcome Measures

Name	Time	Method
Dysphagia >= grade 2	Six months after end of radiotherapy	The rate of observer-reported dysphagia \>= grade 2 measured by the DAHANCA late toxicity score (grade 0-4, with 0 being best)
Xerostomia = grade 4	Six months after end of radiotherapy	The rate of patient-reported xerostomia measured by the EORTC Quality of life questionnaire (QLQ) Head-Neck (HN) 35 (grade 1-4, with 1 being best)

Secondary Outcome Measures

Name	Time	Method
Overall survival	Up to five years after end of radiotherapy	From date of randomisation to date of death
Loco-regional tumor control	Up to five years after end of radiotherapy	Time to event of local-regional failure, from date of randomization to the date of first documented loco-regional failure. Rates are estimated by the Kaplan-Meier method. Interim analyses after 100, 200 and 300 patients. Will not be reported before the primary endpoint.
Disease-specific survival	Up to five years after end of radiotherapy	From date of randomization to date of death (by loco-regional or distant failure)
Late toxicity	From two months to five years after end of radiotherapy	DAHANCA late toxicity score (grade 0-4, 0 being best)
EORTC QLQ-Head-Neck 35	Up to ten years after end of radiotherapy	Swallowing and social-eating scale and specific HN35 items related to eating and pain (grade 1-4, 1 being best)
Number of participants with disease-free survival	Up to five years after end of radiotherapy	From date of randomization to date of death (all causes), loco-regional failure or distant failure, whichever comes first
EORTC C30	Up to ten years after end of radiotherapy	Specific C30 items related to fatigue, nausea and vomiting (grade 1-4, 1 being best)
MD Anderson Dysphagia Index	Up to ten years after end of radiotherapy	MD Anderson Dysphagia Index (MDADI) (grade 1-5, 1 being best)
Stimulated whole-mouth salivary flow	Up to five years after end of radiotherapy	Stimulated whole-mouth salivary flow
Acute toxicity	From the beginning of and up to two months after end of radiotherapy	DAHANCA acute toxicity score (grade 0-4, 0 being best)
Modified barium swallowing	One year after end of radiotherapy	Functional swallowing test - DIGEST scale (grade 0-4, 0 being best)
EuroQol Five Dimension Scale (EQ-5D)	Up to ten years after end of radiotherapy	Quality-adjusted life-years
Composite time corrected toxicity score (CTCT)	Up to five years after end of radiotherapy	The sum of the time corrected dysphagia score and the time corrected xerostomia score normalised to maximum score across all days using EORTC QLQ-Head-Neck 35. The measure is unit-less.

Trial Locations

Locations (7)

Herlev Hospital; 🇩🇰 Copenhagen, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Danish Center for Particle Therapy; 🇩🇰 Aarhus, Denmark

Næstved Hospital; 🇩🇰 Næstved, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark