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

October 23, 2020 updated by: Danish Head and Neck Cancer Group

DAHANCA 35: A Randomized Trial of Proton Versus Photon Radiotherapy for the Treatment of Head-neck Cancer

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)

Study Overview

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 Type

Interventional

Enrollment (Anticipated)

600

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Kenneth Jensen, MD, PhD
  • Phone Number: +45 78456400
  • Email: kennjens@rm.dk

Study Locations

      • Aalborg, Denmark
        • Recruiting
        • Aalborg University Hospital
        • Contact:
          • Maria Andersen, MD
        • Contact:
          • Martin S Nielsen, MSc
      • Aarhus, Denmark
        • Recruiting
        • Aarhus University Hospital
        • Contact:
          • Jesper Eriksen, MD, PhD
        • Contact:
          • Jørgen BB Petersen, MSc
      • Aarhus, Denmark
        • Recruiting
        • Danish Center for Particle Therapy
        • Contact:
          • Kenneth Jensen, MD, PhD
      • Copenhagen, Denmark
        • Recruiting
        • Rigshospitalet
        • Contact:
          • Jeppe Friborg, MD, PhD
        • Contact:
          • Bob Smulders, MSc
      • Copenhagen, Denmark
        • Recruiting
        • Herlev Hospital
        • Contact:
          • Elo Andersen, MD
      • Næstved, Denmark
        • Recruiting
        • Næstved Hospital
        • Contact:
          • Mohammad Farhadi, MD
        • Contact:
          • Eva Samsøe, MSc, PhD
      • Odense, Denmark
        • Recruiting
        • Odense University Hospital
        • Contact:
          • Jørgen Johansen, MD, PhD
        • Contact:
          • Christian R Hansen, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Proton radiotherapy
Active Comparator: 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
Photon radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dysphagia >= grade 2
Time Frame: 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)
Six months after end of radiotherapy
Xerostomia = grade 4
Time Frame: 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)
Six months after end of radiotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Loco-regional tumor control
Time Frame: 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.
Up to five years after end of radiotherapy
Overall survival
Time Frame: Up to five years after end of radiotherapy
From date of randomisation to date of death
Up to five years after end of radiotherapy
Number of participants with disease-free survival
Time Frame: 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
Up to five years after end of radiotherapy
Disease-specific survival
Time Frame: Up to five years after end of radiotherapy
From date of randomization to date of death (by loco-regional or distant failure)
Up to five years after end of radiotherapy
Acute toxicity
Time Frame: From the beginning of and up to two months after end of radiotherapy
DAHANCA acute toxicity score (grade 0-4, 0 being best)
From the beginning of and up to two months after end of radiotherapy
Late toxicity
Time Frame: From two months to five years after end of radiotherapy
DAHANCA late toxicity score (grade 0-4, 0 being best)
From two months to five years after end of radiotherapy
EORTC QLQ-Head-Neck 35
Time Frame: 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)
Up to ten years after end of radiotherapy
EORTC C30
Time Frame: Up to ten years after end of radiotherapy
Specific C30 items related to fatigue, nausea and vomiting (grade 1-4, 1 being best)
Up to ten years after end of radiotherapy
MD Anderson Dysphagia Index
Time Frame: Up to ten years after end of radiotherapy
MD Anderson Dysphagia Index (MDADI) (grade 1-5, 1 being best)
Up to ten years after end of radiotherapy
EuroQol Five Dimension Scale (EQ-5D)
Time Frame: Up to ten years after end of radiotherapy
Quality-adjusted life-years
Up to ten years after end of radiotherapy
Composite time corrected toxicity score (CTCT)
Time Frame: 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.
Up to five years after end of radiotherapy
Modified barium swallowing
Time Frame: One year after end of radiotherapy
Functional swallowing test - DIGEST scale (grade 0-4, 0 being best)
One year after end of radiotherapy
Stimulated whole-mouth salivary flow
Time Frame: Up to five years after end of radiotherapy
Stimulated whole-mouth salivary flow
Up to five years after end of radiotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jeppe Friborg, MD, PhD, Danish Head-Neck Cancer Group (DAHANCA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2020

Primary Completion (Anticipated)

March 1, 2025

Study Completion (Anticipated)

September 1, 2025

Study Registration Dates

First Submitted

October 19, 2020

First Submitted That Met QC Criteria

October 23, 2020

First Posted (Actual)

October 29, 2020

Study Record Updates

Last Update Posted (Actual)

October 29, 2020

Last Update Submitted That Met QC Criteria

October 23, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAHANCA 35

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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