Head and Neck NeoplasmsPhase 3UPGRADE-RTNCT02442375
Uniform FDG-PET Guided Gradient Dose Prescription to Reduce Late Radiation Toxicity
A Phase 3 study testing standard dose prescription and FDG-PET guided gradient dose prescription in people with Head and Neck Neoplasms and Carcinoma, Squamous Cell, run by Radboud University Medical Center at 5 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Head and Neck Neoplasms, Carcinoma, Squamous Cell
- What is being tested?
- standard dose prescription and FDG-PET guided gradient dose prescription
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 5 sitesNetherlands
- Study dates
- Jun 2016to 3 Jul 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites
VU University Medical Center Amsterdam
Amsterdam
Radiotherapiegroep, Arnhem
Arnhem
MAASTRO clinic, Maastricht
Maastricht
Radboud University Nijmegen Medical Center
Nijmegen
University Medical Center Utrecht
Utrecht
About this study
Official title: Uniform FDG-PET Guided GRAdient Dose prEscription to Reduce Late Radiation Toxicity (UPGRADE-RT): a Randomised Controlled Trial With Dose Reduction to the Elective Neck in Head and Neck Squamous Cell Carcinoma
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
- Conditions
- Head and Neck Neoplasms, Carcinoma, Squamous Cell
- Being tested
- standard dose prescription, FDG-PET guided gradient dose prescription
- Keywords
- head and neck cancer, accelerated radiotherapy, dose reduction, dose de-escalation, elective lymph nodes, FDG-PET
- Medical subject headings
- Head and Neck Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
standard dose prescriptionRadiation
- standard elective dose
- no intermediate dose-level
- visual interpretation of FDG-PET-scan
FDG-PET guided gradient dose prescriptionRadiation
- de-escalation of elective dose
- intermediate dose-level
- standardized methods to evaluate FDG-PET-scan
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Radiation: FDG-PET guided gradient dose prescription |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity: normalcy of diet (score of the performance status scale for head and neck cancer patients)
Measured: 12 months
Secondary outcomes (1)
Safety: recurrence in electively irradiated lymph nodes
A Kaplan-Meier estimate will be calculated
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study startJun 2016
- Primary completion3 Jul 2024
- Study completion3 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Head and Neck NeoplasmsStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht, Amsterdam UMC, location VUmc, Maastro Clinic, The Netherlands, Radiotherapiegroep
- Responsible party
- Sponsor
- Investigators
- Prof. Dr. J.H.A.M. Kaanders, Study chair, Radboud University Nijmegen Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442375
- Sponsor's protocol ID
- UPGRADE-RT v3.5 dd20201201
- Acronym
- UPGRADE-RT
- Status last verified
- Oct 2025
- First submitted
- 21 Apr 2015
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40233286van 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.
PubMed 41057084van 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.
PubMed 28327089
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uniform FDG-PET Guided GRAdient Dose prEscription to Reduce Late Radiation Toxicity (UPGRADE-RT): a Randomised Controlled Trial With Dose Reduction to the Elective Neck in Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02442375
- Acronym / sponsor ID
- UPGRADE-RT / UPGRADE-RT v3.5 dd20201201
- Conditions
- Head and Neck Neoplasms, Carcinoma, Squamous Cell
- Keywords
- head and neck cancer, accelerated radiotherapy, dose reduction, dose de-escalation, elective lymph nodes, FDG-PET
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- UMC Utrecht, Amsterdam UMC, location VUmc, Maastro Clinic, The Netherlands, Radiotherapiegroep
- Study start
- Jun 2016 (actual)
- Primary completion
- 3 Jul 2024 (actual)
- Study completion
- 3 Jul 2024 (actual)
- First posted
- 13 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard dose prescription | Active comparator | Radiation: standard dose prescription* FDG-PET-scan in treatment mask for radiotherapy planning * Accelerated radiotherapy IMRT/VMAT with SIB (34 fraction in 5.5 weeks) |
| FDG-PET guided gradient dose prescription | Experimental | Radiation: FDG-PET guided gradient dose prescription* FDG-PET-scan in treatment mask for radiotherapy planning * Accelerated radiotherapy IMRT/VMAT with SIB (34 fraction in 5.5 weeks) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| standard dose prescription* standard elective dose * no intermediate dose-level * visual interpretation of FDG-PET-scan | Radiation | standard dose prescription |
| FDG-PET guided gradient dose prescription* de-escalation of elective dose * intermediate dose-level * standardized methods to evaluate FDG-PET-scan | Radiation | FDG-PET guided gradient dose prescription |
Primary outcome
Toxicity: normalcy of diet (score of the performance status scale for head and neck cancer patients)
Time frame: 12 months
1 secondary outcome
Safety: recurrence in electively irradiated lymph nodes
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- Results publication: PubMed 40233286van 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.
- Results publication: PubMed 41057084van 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.
- Derived from this study: PubMed 28327089van 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. Dr. J.H.A.M. Kaanders study chair
Radboud University Nijmegen Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing standard dose prescription and FDG-PET guided gradient dose prescription in people with Head and Neck Neoplasms and Carcinoma, Squamous Cell, run by Radboud University Medical Center at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity: normalcy of diet (score of the performance status scale for head and neck cancer patients) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02442375, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.