Squamous Cell Carcinoma of the Head and NeckERM-PT-HNSCCNCT03513042
Early Response Evaluation of Proton Therapy by PET-imaging in Squamous Cell Carcinoma Located in the Head and Neck
An observational study of Squamous Cell Carcinoma of the Head and Neck, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
The goal of this project is to develop and characterise an imaging strategy for biology-guided individualisation of the proton therapy plan to improve patient outcome and quality-of-life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy
- Type of treatment
- Surgery or procedure
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Jan 2021to 23 Nov 2022
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: In the Netherlands, 85% of patients that will be treated by PT , which includes HNSCC-patients, will be selected using a model-based approach (MBA). For every potential PT-patient an in silico comparison between a PT-plan and XRT-plan will be made to determine the amount of dose to relevant organs at risk (OARs). Using models of normal tissue complication probability (NTCP), which describe the relationship between dose and the risk of complications, the difference in NTCP ( NTCP) between PT and XRT is estimated. Cases that surpass a predefined threshold and thus are expected to significantly suffer from less toxicity from PT than XRT, will be accepted for PT and form the base population of this study.
Who may be able to join
- In order to be eligible to participate in this study, a subject must meet all following criteria:
- has reached adult age (≥ 18 years) at time of signing informed consent;
- is diagnosed with primary, cytologically/histologically proven, unresected invasive HNSCC;
- has at least one measurable lesion at baseline CT/MRI larger than 2 cm in diameter;
- is eligible for and thus candidate for PT ± systemic therapy with curative intent (for locally advanced HNSCC);
- has a life expectancy of at least 3 months;
- is expected able to undergo and willing to participate in all study and clinical procedures;
- has provided legal informed consent according to ICH/GCP and national/local regulations.
Who cannot join
- A potential subject who meets any of the following criteria will be (secondarily) excluded:
- has known presence of distant metastases;
- suffers from paranasal sinus, salivary cancer, or thyroid malignancies;
- had prior chemotherapy within the last 3 years which is considered influencing tumour biology, proposed treatment or outcome (site investigator discretion);
- had previous surgical resection for the same disease;
- had any prior radiotherapy to the head and neck region within the last 3 years which is considered influencing tumour biology, proposed treatment or outcome (site investigator discretion);
Show all 21Show fewer
- suffers any other prior (5 years) or current malignancy (except for basal/squamous cell skin cancer, lentigo maligna, surgically cured carcinoma in situ of the cervix, in situ breast cancer or incidental finding of stage T1a-T1b prostate cancer) or serious (psychiatric) disease at study entry that could affect the treatment, evaluation or outcome of current HSCC e.g. a Karnofsky Performance Score <60 / ECOG Performance Status >2 (left to the discretion of the SI entering patient in the study);
- has uncontrolled diabetes mellitus resulting in a fasting hyperglycaemia ≥11.1 mmol.L-1 (≥200 mg.dL-1) at time of 18F-FDG PET-CT and rescheduling this investigation within the set time-window is not possible. The use of short-acting insulins within 4 h of the 18F-FDG PET scan is not allowed;
- has evidence of infection localised to the neck in the 14 days prior to 18F-FDG PET-CT;
- cannot undergo each baseline PET-CT investigations within 28 days and the start of PT;
- underwent biopsy of tumour of lymph nodes in the 14 days prior to the PET-CT scan that could interfere with imaging (left to the discretion of the PI entering patient in the study);
- is unable to tolerate lying supine for the duration of a PET-CT examination;
- is known pregnant/lactating at time of PET-CT. A negative test is not obligatory;
- specific for activation PET-CT: is scheduled to be treated in Gantry-2 (nearest to PET-CT scanner), is mobile and in case of multiple beams, only patients irradiated with a maximum angle between two beams of 90º are eligible;
- suffers from (severe) claustrophobia. Low dose benzodiazepines are allowed;
- has a history of allergic reaction or hypersensitivity attributed to compounds of similar chemical or biologic composition to 18F-FDG or 18F-FAZA (extremely unlikely);
- is known with a condition resulting in high radiation sensitivity (e.g. ataxia telangiectasia, Nijmegen Breakage Syndrome, DNA LIG4-deficiency, Fanconi anaemia [68]);
- has a known adequate renal function (creatinine clearance ≥60 mL/min/1.73m2).
- is not proficient in the Dutch or English language or has access to unbiased translators that can aid in the study procedures or clinical questionnaires;
- is unwilling or unable to provide legal informed consent (e.g. incapacitated adult), a serious (mental) condition arises, which questions persistence of informed consent, or withdraws (part) of his/her informed consent;
- in case a patient already participates in another imaging study (especially when involving additional ionising radiation such as CT-imaging), the cumulative (radiation) burden should be discussed with the PI; Participation to other than routine PT schemes (paragraph 4.4) is not an exclusion criterion per se and should be evaluated case-by-case by the coordinating investigator.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Holland Proton Therapy Centre (HollandPTC)
Delft, South Holland, 2629 JH
About this study
The goal of this project is to develop and characterise an imaging strategy for biology-guided individualisation of the proton therapy plan to improve patient outcome and quality-of-life.
Positron-emission tomography (PET) studies reflecting glucose metabolism, hypoxia and physical changes of proton-irradiated tumour tissues will be performed. Patients with head and neck cancer will be studied, as these individuals frequently experience recurrences within the radiation field, often with limited therapeutic options. Severe side-effects and functional impairment, deteriorating patients' quality-of-life, limited the use of dose-escalation in recent feasibility studies of photon therapy guided by individual PET-response. However, proton therapy, currently being introduced in the Netherlands, improves the precision of radiotherapy and thereby limits the side-effects caused by irradiation of neighbouring healthy tissues. Therefore, in proton therapy dose-escalation to improve patient outcome is less restricted by toxicity.
Read more
Using PET-studies of two hallmarks of radioresistance, glucose metabolism and hypoxia, side-by-side, before and early in-treatment, the predictive ability of both PET-techniques for local recurrence-free survival will be compared. A treatment plan adapted to the individual response measured by both procedures and compute tumour-dose and toxicity, will be simulated, thereby substantiating feasibility of image-guided adaptive replanning. Simultaneously to biological responses, proton therapy-induced physical changes will be studied. These atomic changes, dependent on tissue-composition and dose-deposition, are measurable by PET. It is expected that activation-PET to measure tissue-changes during therapy, a potential new biomarker of treatment efficacy, toxicity but also accuracy of treatment plan execution. Activation-PET will be related to earlier-mentioned PET-imaging of metabolism.
This clinical-technological project paves the way for an interventional trial of PET-guided treatment personalisation. Activation-PET will also serve as biomarker and quality control for proton therapy and support the current development of specialised in-beam PET-technology. These PET-techniques together will help us to individualise treatment, which is of great importance for the success and cost-effectiveness of proton therapy.
Read the detailed description
Rationale: Proton therapy (PT), currently being introduced in the Netherlands, delivers radiation dose more conformal than photon radiotherapy, therefore healthy tissue damage is expected to be lower and at least similar tumouricidal effects are described. This increases the therapeutic window of radiotherapy which could be used for intensified treatment to patients prone to locoregional failure. From photon radiotherapy it is known that stratification of patients with head and neck squamous cell carcinoma (HNSCC) is possible using different positron-emission tomography (PET-)techniques. Distribution of tumour hypoxia, a main cause of resistance to radiotherapy, and glucose metabolic need have been described. PT, in contrast to photon therapy, results in activation of endogenous atoms in the irradiated tissues which can be measured using PET and reflect dose deposition and tissue composition. This provides a unique application of PET in this treatment modality as quality assurance of proton therapy and potentially as biomarker of tissue response to proton therapy. The main hypothesis is that early during PT, PET is capable of discerning a subset of patients with increased risk of locoregional failure with a univariate hazard-ratio of at least 4.0. At this time point, treatment intensification would still be possible.
Objective: To assess whether early changes in hypoxia between baseline and in the (end of the) second week of proton therapy are predictive for time-to-local recurrence in patients with HNSCC (primary). Secondary objectives include: to compare the role of hypoxia-PET to more readily available PET of glucose metabolism, to describe spatial conformity between the PET-scan and the location of the recurrence, to determine the potential of adaptive replanning based on two-timepoint PET-imaging. In a pilot setting the feasibility of activation PET in a clinical setting for quality assurance of PT-plans and potential biomarker of PT-induced tissue changes will be explored.
Study design: Prospective, single-arm, observational cohort study with invasive measurements.
Study population: Adults diagnosed with primary, unresected invasive HNSCC, planned for PT ± systemic therapy with curative intent with at least one measurable lesion larger than 2 cm at baseline (n=40).
Intervention: All patients are asked to undergo one additional baseline 18F-FAZA PET-scan (hypoxia) at baseline 18F-FDG PET-imaging (glucose metabolism) is already performed during clinical work-up. Both 18F-FAZA and 18F-FDG PET-scans will be repeated in the (end of the) second week of PT, unless no hypoxia is witnessed at baseline, then only the 18F-FDG PET-scan is repeated. In a pilot setting, 10 patients are asked to further undergo activation PET-scanning immediately after PT in the first, second and last week.
Main study parameters/endpoints: The main study parameters are the percent change in hypoxic tumour volume between baseline PET and interim PET of hypoxia and the percent change in total lesion glycolysis between baseline PET and interim PET of glucose metabolism. The primary endpoint is 3-year local recurrence-free survival (LRFS).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Each PET-acquisition will be performed in radiotherapy position preferably using fixation devices (mould mask). The procedures of PET-imaging of 18F-FAZA (hypoxia) and 18F-FDG (glucose metabolism) each involve preparation (hypoxia: none, glucose metabolism: 6h fasted), intravenous injection of a radiopharmaceutical, a waiting period in solitude (hypoxia: 2 h, glucose metabolism: 1 h), followed by PET-acquisition (hypoxia: 10-20 min, glucose metabolism: 5-10 min). Occurrence of infusion-related reactions (e.g. allergy) is highly unlikely. The radiation burden attached to each of these procedures are 6.8 mSv (hypoxia) and 2.9 mSv (glucose metabolism). The pilot substudy requires immediate transfer from PT-gantry to scanner followed by a 30-min PET-acquisition three times, resulting in an additional radiation burden of ~0.5 mSv per procedure. All other procedures are part of clinical protocol. There will be no individual benefit for enrolled subjects. Financial compensation for study-related travel expenses have been arranged. However, where possible, each study procedure will be combined with a regular visit to the PT-facility.
- Being tested
- Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy
- Keywords
- intensity-modulated proton therapy, therapy response evaluation, positron emission tomography (PET), hypoxia, metabolism, 18F-fluoroazomycin-arabinoside (FAZA), 18F-2-fluoro-2-deoxy-D-glucose (FDG), head and neck neoplasms, image-guided proton therapy, treatment outcome, predictive biomarker
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Hypoxia, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensity Modulated Proton Therapy (IMPT) +/- ChemotherapyRadiation
Standard of care:
- IMPT (conventional fractionation [35x1,55/2Gy, 5 fractions/week] or accelerated fractionation [35x1,55/2Gy, 6 fractions/week])
- with or without concurrent cisplatin (100 mg/m2 [d1, d22 and d43] or 40 mg/m2 weekly) or cetuximab (weekly 400 mg/m2 in 2h followed by 250 mg/m2 in 1h)
| Study group | Role | What they receive |
|---|---|---|
| Cohort | Intervention:
- Standard of care Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy.
Baseline measurements:
- All patients undergo baseline FDG PET-CT and FAZA PET-CT of the head-neck area.
Interim measurements conventional):
* FDG PET-CT will be repeated at the end of the second week of IMPT.
* FAZA PET will only be repeated at the end of the second week of IMPT if a hypoxic tumour volume was found at baseline scanning.
* A subcohort will also undergo activation PET imaging three times during IMPT. Receives: Radiation: Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year local recurrence-free survival (LRFS)
This is defined as the length of time (days) that the patient survives since study registration without any signs or symptoms of locoregional HNSCC assessed by structured clinical and radiological (clinical) follow-up (paragraph 8.5). If at close-out date of the study, there are no signs of locoregional recurrence, the patient will be censored to the date of the most recent follow-up examination. Distant recurrence/progression and second cancers diagnosed before locoregional recurrence and death in absence of locoregional recurrence are not considered events of interest, but will be considered as competing risk events in the analysis of this endpoint. The 2-year cumulative incidence rates will be estimated from the curves and its associated 95% confidence intervals will be calculated.
Measured: 3 years after start of IMPT
Secondary outcomes (4)
3-year overall survival
similar to LRFS but 'death from any cause' will be the event of interest
Measured: 3 years after start of IMPT
3-year disease-specific survival
similar to LRFS but 'death from HNSCC' will be the event of interest
Measured: 3 years after start of IMPT
3-year disease-free survival
similar to LRFS but 'any recurrence (including systemic)' will be the event of interest
Measured: 3 years after start of IMPT
tumour response per RECIST
Response Evaluation Criteria In Solid Tumours (RECIST v1.1) tumour response during structured radiological follow-up
Measured: 3 years after start of IMPT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2018
- Study start21 Jan 2021
- Primary completion23 Nov 2022
- Study completion23 Nov 2022
Why it stopped: Inclusionrate dropped due to changes in clinical process
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Leiden 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- HollandPTC
- Responsible party
- Principal investigator, Dennis Vriens, MD, PhD, Leiden University Medical Center
- Investigators
- Dennis Vriens, MD, PhD, Study chair, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03513042
- Sponsor's protocol ID
- NL63825.058.17
- Other IDs
- 916.18.008, P17.291
- Acronym
- ERM-PT-HNSCC
- Status last verified
- Dec 2022
- First submitted
- 19 Apr 2018
- Last updated
- 6 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: raw data will be made publicly available as required by the funding body. A datamanagement plan including public sharing is available on request.
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Response Evaluation of Proton Therapy by PET-imaging in Squamous Cell Carcinoma Located in the Head and Neck
- ClinicalTrials.gov ID
- NCT03513042
- Acronym / sponsor ID
- ERM-PT-HNSCC / NL63825.058.17
- Keywords
- intensity-modulated proton therapy, therapy response evaluation, positron emission tomography (PET), hypoxia, metabolism, 18F-fluoroazomycin-arabinoside (FAZA), 18F-2-fluoro-2-deoxy-D-glucose (FDG), head and neck neoplasms
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Inclusionrate dropped due to changes in clinical process
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- HollandPTC
- Study start
- 21 Jan 2021 (actual)
- Primary completion
- 23 Nov 2022 (actual)
- Study completion
- 23 Nov 2022 (actual)
- First posted
- 1 May 2018 (actual)
- 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 goal of this project is to develop and characterise an imaging strategy for biology-guided individualisation of the proton therapy plan to improve patient outcome and quality-of-life.
Positron-emission tomography (PET) studies reflecting glucose metabolism, hypoxia and physical changes of proton-irradiated tumour tissues will be performed. Patients with head and neck cancer will be studied, as these individuals frequently experience recurrences within the radiation field, often with limited therapeutic options. Severe side-effects and functional impairment, deteriorating patients' quality-of-life, limited the use of dose-escalation in recent feasibility studies of photon therapy guided by individual PET-response. However, proton therapy, currently being introduced in the Netherlands, improves the precision of radiotherapy and thereby limits the side-effects caused by irradiation of neighbouring healthy tissues. Therefore, in proton therapy dose-escalation to improve patient outcome is less restricted by toxicity.
Using PET-studies of two hallmarks of radioresistance, glucose metabolism and hypoxia, side-by-side, before and early in-treatment, the predictive ability of both PET-techniques for local recurrence-free survival will be compared. A treatment plan adapted to the individual response measured by both procedures and compute tumour-dose and toxicity, will be simulated, thereby substantiating feasibility of image-guided adaptive replanning. Simultaneously to biological responses, proton therapy-induced physical changes will be studied. These atomic changes, dependent on tissue-composition and dose-deposition, are measurable by PET. It is expected that activation-PET to measure tissue-changes during therapy, a potential new biomarker of treatment efficacy, toxicity but also accuracy of treatment plan execution. Activation-PET will be related to earlier-mentioned PET-imaging of metabolism.
This clinical-technological project paves the way for an interventional trial of PET-guided treatment personalisation. Activation-PET will also serve as biomarker and quality control for proton therapy and support the current development of specialised in-beam PET-technology. These PET-techniques together will help us to individualise treatment, which is of great importance for the success and cost-effectiveness of proton therapy.
Detailed description
Rationale: Proton therapy (PT), currently being introduced in the Netherlands, delivers radiation dose more conformal than photon radiotherapy, therefore healthy tissue damage is expected to be lower and at least similar tumouricidal effects are described. This increases the therapeutic window of radiotherapy which could be used for intensified treatment to patients prone to locoregional failure. From photon radiotherapy it is known that stratification of patients with head and neck squamous cell carcinoma (HNSCC) is possible using different positron-emission tomography (PET-)techniques. Distribution of tumour hypoxia, a main cause of resistance to radiotherapy, and glucose metabolic need have been described. PT, in contrast to photon therapy, results in activation of endogenous atoms in the irradiated tissues which can be measured using PET and reflect dose deposition and tissue composition. This provides a unique application of PET in this treatment modality as quality assurance of proton therapy and potentially as biomarker of tissue response to proton therapy. The main hypothesis is that early during PT, PET is capable of discerning a subset of patients with increased risk of locoregional failure with a univariate hazard-ratio of at least 4.0. At this time point, treatment intensification would still be possible.
Objective: To assess whether early changes in hypoxia between baseline and in the (end of the) second week of proton therapy are predictive for time-to-local recurrence in patients with HNSCC (primary). Secondary objectives include: to compare the role of hypoxia-PET to more readily available PET of glucose metabolism, to describe spatial conformity between the PET-scan and the location of the recurrence, to determine the potential of adaptive replanning based on two-timepoint PET-imaging. In a pilot setting the feasibility of activation PET in a clinical setting for quality assurance of PT-plans and potential biomarker of PT-induced tissue changes will be explored.
Study design: Prospective, single-arm, observational cohort study with invasive measurements.
Study population: Adults diagnosed with primary, unresected invasive HNSCC, planned for PT ± systemic therapy with curative intent with at least one measurable lesion larger than 2 cm at baseline (n=40).
Intervention: All patients are asked to undergo one additional baseline 18F-FAZA PET-scan (hypoxia) at baseline 18F-FDG PET-imaging (glucose metabolism) is already performed during clinical work-up. Both 18F-FAZA and 18F-FDG PET-scans will be repeated in the (end of the) second week of PT, unless no hypoxia is witnessed at baseline, then only the 18F-FDG PET-scan is repeated. In a pilot setting, 10 patients are asked to further undergo activation PET-scanning immediately after PT in the first, second and last week.
Main study parameters/endpoints: The main study parameters are the percent change in hypoxic tumour volume between baseline PET and interim PET of hypoxia and the percent change in total lesion glycolysis between baseline PET and interim PET of glucose metabolism. The primary endpoint is 3-year local recurrence-free survival (LRFS).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Each PET-acquisition will be performed in radiotherapy position preferably using fixation devices (mould mask). The procedures of PET-imaging of 18F-FAZA (hypoxia) and 18F-FDG (glucose metabolism) each involve preparation (hypoxia: none, glucose metabolism: 6h fasted), intravenous injection of a radiopharmaceutical, a waiting period in solitude (hypoxia: 2 h, glucose metabolism: 1 h), followed by PET-acquisition (hypoxia: 10-20 min, glucose metabolism: 5-10 min). Occurrence of infusion-related reactions (e.g. allergy) is highly unlikely. The radiation burden attached to each of these procedures are 6.8 mSv (hypoxia) and 2.9 mSv (glucose metabolism). The pilot substudy requires immediate transfer from PT-gantry to scanner followed by a 30-min PET-acquisition three times, resulting in an additional radiation burden of ~0.5 mSv per procedure. All other procedures are part of clinical protocol. There will be no individual benefit for enrolled subjects. Financial compensation for study-related travel expenses have been arranged. However, where possible, each study procedure will be combined with a regular visit to the PT-facility.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort | – | Radiation: Intensity Modulated Proton Therapy (IMPT) +/- ChemotherapyIntervention: - Standard of care Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy. Baseline measurements: - All patients undergo baseline FDG PET-CT and FAZA PET-CT of the head-neck area. Interim measurements conventional): * FDG PET-CT will be repeated at the end of the second week of IMPT. * FAZA PET will only be repeated at the end of the second week of IMPT if a hypoxic tumour volume was found at baseline scanning. * A subcohort will also undergo activation PET imaging three times during IMPT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- In the Netherlands, 85% of patients that will be treated by PT , which includes HNSCC-patients, will be selected using a model-based approach (MBA). For every potential PT-patient an in silico comparison between a PT-plan and XRT-plan will be made to determine the amount of dose to relevant organs at risk (OARs). Using models of normal tissue complication probability (NTCP), which describe the relationship between dose and the risk of complications, the difference in NTCP ( NTCP) between PT and XRT is estimated. Cases that surpass a predefined threshold and thus are expected to significantly suffer from less toxicity from PT than XRT, will be accepted for PT and form the base population of this study.
Key inclusion criteria (8 listed)
- In order to be eligible to participate in this study, a subject must meet all following criteria:
- has reached adult age (≥ 18 years) at time of signing informed consent;
- is diagnosed with primary, cytologically/histologically proven, unresected invasive HNSCC;
- has at least one measurable lesion at baseline CT/MRI larger than 2 cm in diameter;
- is eligible for and thus candidate for PT ± systemic therapy with curative intent (for locally advanced HNSCC);
Key exclusion criteria (21 listed)
- A potential subject who meets any of the following criteria will be (secondarily) excluded:
- has known presence of distant metastases;
- suffers from paranasal sinus, salivary cancer, or thyroid malignancies;
- had prior chemotherapy within the last 3 years which is considered influencing tumour biology, proposed treatment or outcome (site investigator discretion);
- had previous surgical resection for the same disease;
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 |
|---|---|---|
| Intensity Modulated Proton Therapy (IMPT) +/- ChemotherapyStandard of care: * IMPT (conventional fractionation [35x1,55/2Gy, 5 fractions/week] or accelerated fractionation [35x1,55/2Gy, 6 fractions/week]) * with or without concurrent cisplatin (100 mg/m2 [d1, d22 and d43] or 40 mg/m2 weekly) or cetuximab (weekly 400 mg/m2 in 2h followed by 250 mg/m2 in 1h) | Radiation | Cohort |
Primary outcome
3-year local recurrence-free survival (LRFS)
Time frame: 3 years after start of IMPT
This is defined as the length of time (days) that the patient survives since study registration without any signs or symptoms of locoregional HNSCC assessed by structured clinical and radiological (clinical) follow-up (paragraph 8.5). If at close-out date of the study, there are no signs of locoregional recurrence, the patient will be censored to the date of the most recent follow-up examination. Distant recurrence/progression and second cancers diagnosed before locoregional recurrence and death in absence of locoregional recurrence are not considered events of interest, but will be considered as competing risk events in the analysis of this endpoint. The 2-year cumulative incidence rates will be estimated from the curves and its associated 95% confidence intervals will be calculated.
4 secondary outcomes
3-year overall survival
Time frame: 3 years after start of IMPT
3-year disease-specific survival
Time frame: 3 years after start of IMPT
3-year disease-free survival
Time frame: 3 years after start of IMPT
tumour response per RECIST
Time frame: 3 years after start of IMPT
Results and safety
The study was stopped early (reason given: Inclusionrate dropped due to changes in clinical process). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2022.
- Holland Proton Therapy Centre (HollandPTC)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. raw data will be made publicly available as required by the funding body. A datamanagement plan including public sharing is available on request.
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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.
Dennis Vriens, MD, PhD study chair
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Squamous Cell Carcinoma of the Head and Neck, run by Leiden University Medical Center at 1 site 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 21 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: stopped early, as of the sponsor's last update on 6 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study was stopped early (reason given: Inclusionrate dropped due to changes in clinical process). Results are not available in the source record.
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?
3-year local recurrence-free survival (LRFS) (time frame: 3 years after start of IMPT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Dec 2022; AzTrials last refreshed its copy on 7 Nov 2026.