NCT02442375

Brief Summary

The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and introduction of an intermediate dose-level in the treatment of head and neck cancer will results in less radiation sequelae and improved quality of life after treatment whilst the recurrence rate in electively irradiated lymph nodes should not be compromised. The full study protocol can be found here: https://doi.org/10.1200/jco-24-02194

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
300

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 2016

Longer than P75 for phase_3

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 21, 2015

Completed
22 days until next milestone

First Posted

Study publicly available on registry

May 13, 2015

Completed
1.1 years until next milestone

Study Start

First participant enrolled

June 1, 2016

Completed
8.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 3, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 3, 2024

Completed
Last Updated

November 18, 2025

Status Verified

October 1, 2025

Enrollment Period

8.1 years

First QC Date

April 21, 2015

Last Update Submit

November 14, 2025

Conditions

Head and Neck NeoplasmsCarcinoma, Squamous Cell

Keywords

head and neck canceraccelerated radiotherapydose reductiondose de-escalationelective lymph nodesFDG-PET

Outcome Measures

Primary Outcomes (1)

  • Toxicity: normalcy of diet (score of the performance status scale for head and neck cancer patients)

    12 months

Secondary Outcomes (1)

  • Safety: recurrence in electively irradiated lymph nodes

    24 months

Other Outcomes (10)

  • Acute toxicity (common toxicity criteria v2.0)

    up to 3 months

  • Late toxicity: swallowing function (water swallowing test)

    3, 12 and 24 months

  • Late toxicity: salivary gland function (stimulated flow rates)

    3, 12 and 24 months

  • +7 more other outcomes

Study Arms (2)

standard dose prescription

ACTIVE COMPARATOR

* FDG-PET-scan in treatment mask for radiotherapy planning * Accelerated radiotherapy IMRT/VMAT with SIB (34 fraction in 5.5 weeks)

Radiation: standard dose prescription

FDG-PET guided gradient dose prescription

EXPERIMENTAL

* FDG-PET-scan in treatment mask for radiotherapy planning * Accelerated radiotherapy IMRT/VMAT with SIB (34 fraction in 5.5 weeks)

Radiation: FDG-PET guided gradient dose prescription

Interventions

standard dose prescriptionRADIATION

* standard elective dose * no intermediate dose-level * visual interpretation of FDG-PET-scan

standard dose prescription
FDG-PET guided gradient dose prescriptionRADIATION

* de-escalation of elective dose * intermediate dose-level * standardized methods to evaluate FDG-PET-scan

FDG-PET guided gradient dose prescription

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Newly diagnosed tumours classified as stage T2-4 N0-2 (TNM 7th edition 2009) located in the larynx, oropharynx or hypopharynx (unknown primary and oral cavity are not eligible)
  • Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumour
  • Decision for curative intent external beam radiotherapy with elective treatment of the neck made by a multidisciplinary head-and-neck oncology team. The patient must be expected to complete the treatment.
  • Radiotherapy planned to start within 6 weeks from baseline imaging of tumour assessment
  • No distant metastasis (M0) (TNM 7th edition 2009)
  • WHO performance status 0-2
  • ≥ 18 years of age
  • Written informed consent

You may not qualify if:

  • Concomitant chemotherapy or EGFR inhibitors for this tumour.
  • Primary tumour of the oral cavity or unknown primary tumour
  • Prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumour reductive surgery, neo-adjuvant or concomitant chemotherapy, EGFR inhibitors or radiotherapy), except for endoscopic glottic laser micro surgery.
  • Current participation in any other oncologic interventional clinical study for this tumor.
  • Uncontrolled diabetes mellitus.
  • Known or suspected HIV infection.
  • History of previous malignancy within the last 3 years, with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, basal/squamous cell carcinoma of the skin, and other non-invasive malignancies (e.g. in situ carcinomas)..
  • Any condition (somatic, psychological, familial, sociological or geographical) rendering the patient unable to understand or complete questionnaires.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

VU University Medical Center Amsterdam

Amsterdam, Netherlands

Location

Radiotherapiegroep, Arnhem

Arnhem, Netherlands

Location

MAASTRO clinic, Maastricht

Maastricht, Netherlands

Location

Radboud University Nijmegen Medical Center

Nijmegen, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Related Publications (3)

  • van den Bosch S, Doornaert PAH, Hoebers FJP, Kreike B, Vergeer MR, Zwijnenburg EM, Cox MC, Hannink G, Dijkema T, Kaanders JHAM; Dutch Head and Neck Society. Clinical Benefit and Safety of Reduced Elective Dose in Definitive Radiotherapy for Head and Neck Squamous Cell Carcinoma: The UPGRADE-RT Multicenter Randomized Controlled Trial. J Clin Oncol. 2025 Aug 10;43(23):2583-2594. doi: 10.1200/JCO-24-02194. Epub 2025 Apr 15.

    PMID: 40233286RESULT

  • van den Bosch S, Cox MC, Doornaert PAH, Hoebers FJP, Kreike B, Vergeer MR, Zwijnenburg EM, Hannink G, Dijkema T, Kaanders JHAM; Dutch Head and Neck Society. Dose de-escalation of elective neck irradiation in head and neck cancer: A secondary analysis of acute toxicity findings from the randomized controlled UPGRADE-RT trial. Radiother Oncol. 2025 Dec;213:111196. doi: 10.1016/j.radonc.2025.111196. Epub 2025 Oct 5.

    PMID: 41057084RESULT

  • van den Bosch S, Dijkema T, Kunze-Busch MC, Terhaard CH, Raaijmakers CP, Doornaert PA, Hoebers FJ, Vergeer MR, Kreike B, Wijers OB, Oyen WJ, Kaanders JH. Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma. BMC Cancer. 2017 Mar 21;17(1):208. doi: 10.1186/s12885-017-3195-7.

    PMID: 28327089DERIVED

MeSH Terms

Conditions

Head and Neck NeoplasmsCarcinoma, Squamous Cell

Interventions

Prescriptions

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Pharmaceutical ServicesHealth ServicesHealth Care Facilities Workforce and Services

Study Officials

  • Prof. Dr. J.H.A.M. Kaanders

    Radboud University Nijmegen Medical Center

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 21, 2015

First Posted

May 13, 2015

Study Start

June 1, 2016

Primary Completion

July 3, 2024

Study Completion

July 3, 2024

Last Updated

November 18, 2025

Record last verified: 2025-10

Locations

NL(5)