Head and Neck CancerInGReSNCT05393297
InGReS: Intra-treatment Image Guided Adaptive Radiotherapy Dose-escalation Study
A study testing Imaging: Intra-treatment FDG-PET-CT and MRI and Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation in people with Head and Neck Cancer, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
InGReS is a phase I pilot study of adaptive dose-escalated radiotherapy in combination with platinum-based chemotherapy (CRT) for locally advanced head and neck cancer. InGReS will assess the feasibility of adapting the radiotherapy (RT) plan for each patient, based on anatomical and metabolic changes in the tumour… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Imaging: Intra-treatment FDG-PET-CT and MRI and Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Jun 2022to 16 Jun 2025
- Phase
- Interventional
- 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
Who may be able to join
- Locally advanced, histologically confirmed squamous cell carcinoma (SCC) of the oropharynx and hypopharynx to be treated with primary radical chemo-radiotherapy:
- Hypopharyngeal cancer - HPV negative OR HPV positive
- Oropharyngeal cancer - EITHER HPV negative OR HPV positive with N stage at least N2b and greater than 10 pack year smoking history: All HPV positive oropharyngeal patients should have at least stage III disease (TNM8)
- ≥T2 tumours:
- Staging MRI showing minimum diameter of primary tumour greater than or equal to 1cm
- Staging 18F-FDG-PET/CT showing adequate uptake in the primary tumour, defined as SUVmax of ≥ 5.0
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- Multidisciplinary team (MDT) decision to treat with primary CRT with curative intent
- Patients fit for radical treatment with primary CRT
- WHO Performance Status 0-1
Who cannot join
- Previous radiotherapy to the head and neck region interfering with the protocol treatment plan
- Patients requiring neo-adjuvant chemotherapy
- Inability to tolerate PET or MRI; general contra-indications to MRI
- Contra-indication to gadolinium
- Baseline SUVmax < 5.0 in the primary tumour on PET-CT or smaller than 1cm in axial dimensions on cross sectional imaging
- GFR <40ml/min
- Previous primary malignancy within 2 years (excluding adequately treated non-melanoma skin cancer, low risk Prostate cancer Gleason 6 or below, carcinoma in situ of cervix).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT
Smruti Gorsia, +44 (0)20 7188 2018, smruti.gorsia@gstt.nhs.uk
About this study
InGReS is a phase I pilot study of adaptive dose-escalated radiotherapy in combination with platinum-based chemotherapy (CRT) for locally advanced head and neck cancer.
InGReS will assess the feasibility of adapting the radiotherapy (RT) plan for each patient, based on anatomical and metabolic changes in the tumour seen on MRI and FDG-PET-CT performed after 2 weeks of CRT in a multicentre setting. The overall aim of the trial is to determine the safety and feasibility of delivering dose-escalated Intensity Modulated Radiotherapy (IMRT) to the residual primary tumour, as seen on intra-treatment imaging, in the final 3 weeks of RT.
Read the detailed description
The study will recruit 15 patients with locally advanced oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) who are suitable for primary treatment with concurrent chemo-radiation. The main aim is to see whether it is feasible to perform a FDG positron emission tomography-computed tomography (FDG-PET-CT) and Magnetic Resonance Imaging (MRI) scan after 2 weeks of radiotherapy and re-plan the radiotherapy to escalate the dose of radiotherapy delivered to the residual primary tumour as seen on PET-CT and MRI.
Patients will commence with standard chemo-radiotherapy; 70 Gray (Gy) in 35 fractions with concomitant platinum chemotherapy. After 2 weeks of chemo-radiotherapy patients will have an intra-treatment FDG-PET-CT and MRI scan to assess early response to treatment. Patients with evidence of residual disease will proceed with the dose-escalation phase of the study, with an adaptive radiotherapy re-plan and dose-escalation to the residual primary tumour.
The study will establish acute and late radiotherapy toxicity rates in patients who receive dose-escalated RT, particularly the effect of treatment on long-term swallowing function. The study hypothesis is that mucosal toxicity rates for dose-escalated treatment will be equivalent to those for standard CRT, according to published data. Furthermore, it will also explore whether changes in FDG-PET-CT and MRI during treatment correlate with patient outcomes and potential blood-based biomarkers of treatment response. Local control, disease-free and overall survival will be assessed for both standard and dose-escalated approaches.
- Conditions
- Head and Neck Cancer
- Being tested
- Imaging: Intra-treatment FDG-PET-CT and MRI, Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation
- Keywords
- Radiotherapy, Adaptive, Dose-escalation, Oropharyngeal Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imaging: Intra-treatment FDG-PET-CT and MRIDiagnostic test
FDG-PET-CT and MRI scan will be used during radiotherapy to assess early treatment response and identify tumours eligible for dose-escalation.
Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalationRadiation
Tumours eligible for dose-escalation (boost), as seen on intra-treatment FDG-PET-CT and MRI scan, will receive 76.9 Gy to the residual gross primary tumour. The radiotherapy plan will be replanned to incorporate the simultaneous-integrated-boost to the GTVp which will be delivered over the last 3 weeks of treatment
| Study group | Role | What they receive |
|---|---|---|
| HNSCC receiving (chemo)radiotherapy | Experimental | Radiation: Intra-treatment FDG-PET-CT and MRI will be used to identify tumours and patients for dose-escalation. Patients identified for dose-escalation (boost) will undergo adaptive radiotherapy replanning, with the primary tumour (GTVp) receiving 76.9Gy in 35 fractions. Receives: Diagnostic Test: Imaging: Intra-treatment FDG-PET-CT and MRI; Radiation: Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of delivering an additional 10% dose (biological rather than numerical) of radiotherapy to the residual primary tumour during radiotherapy
Incidence of grade 3 or above late Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC) mucosal toxicity or feeding tube retention rate following completion of treatment. An excess rate of >14% would be regarded as unacceptable.
Measured: 12 months
Secondary outcomes (13)
Incidence of grade 4 acute mucosal toxicity (NCI CTCAE)
Toxicity grading, using National Cancer Institute Common Terminology Criteria for Adverse Events scale v.5.0, will be presented during and up to 12 weeks after treatment. Grading scale: 0-5, with the higher score meaning a worse outcome.
Measured: 12 weeks
Incidence of grade 3 or above late non-mucosal toxicity (NCI CTCAE)
Toxicity of non-mucosal late toxicity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events scale v.5.0. Scores will be presented at 13 weeks; 6 and 12 months after treatment. Grading scale: 0-5, with the higher score meaning a worse outcome.
Measured: 12 months
Incidence of grade 3 or above late non-mucosal toxicity (RTOG/EORTC)
Toxicity of non-mucosal late toxicity will be graded using Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC) late toxicity scoring. Scores will be presented at 13 weeks; 6 and 12 months after treatment. Grading scale: 0-5, with the higher score meaning a worse outcome.
Measured: 12 months
Incidence of grade 3 or above late non-mucosal toxicity (LENT/SOMA criteria)
Toxicity of non-mucosal late toxicity will be graded using the modified Late Effects on Normal Tissues- Subjective, Objective, Management, Analytic (LENTSOMA) scoring systems. Scores will be presented at 13 weeks; 6 and 12 months after treatment. Grading scale: 0-4, with the higher score meaning a worse outcome.
Measured: 12 months
To assess swallowing panel measurements including qualitative swallowing assessments (MDADI)
M.D. Anderson Dysphagia Inventory (MDADI) scores will be plotted over time. Scores will be presented at baseline and weeks 3 \& 7 of CRT. Then at 13 weeks; 6 and 12 months after treatment. A higher MDADI score represents better function and quality of life.
Measured: 12 months
To assess patient reported outcomes measures and quality of life questionnaires (UW-QOL v 4.1)
Patient reported outcomes measures and quality of life scores using the University of Washington Quality of Life Questionnaire (UW-QOL) v4.1 will be plotted over time. Scores will be presented at baseline and weeks 3 \& 7 of CRT. Then at 13 weeks; 6 and 12 months after treatment. A higher score represents better function and quality of life.
Measured: 12 months
To assess patient reported outcomes measures and quality of life questionnaires (EORTC QLQ-C30 and EORTC QLQ-H&N43)
Patient reported outcomes measures and quality of life scores, using the questionnaires of the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Modules 30 and 43 (EORTC QLQ-C30 and EORTC QLQ-H\&N43), will be plotted over time. Scores will be presented at baseline and weeks 3 \& 7 of CRT. Then at 13 weeks; 6 and 12 months after treatment.
For the functioning and the quality of life scales, a higher score indicates better health. For the symptoms scales, a higher score indicates a higher level of symptom burden.
Measured: 12 months
To assess results of quantitative swallowing assessments (Videofluoroscopy)
Video-fluoroscopy test scores, particularly the Rosenbek Penetration/Aspiration Scale (PAS) and the summary Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scores, will be presented at 12 months after treatment. For both PAS and summary DIGEST scores, a higher score indicates worse function.
Measured: 12 months
To assess late toxicity rates and the effect of treatment on swallowing function (100ml water swallow)
100ml water swallow test results will be presented at baseline. Then at 6 weeks, 13 weeks, 6 months and 12 months after treatment. Patients will be reported as having failed the test if they coughed or had a wet voice quality post swallow or were unable to finish the task.
Measured: 12 months
To assess tumour response to adaptive radiotherapy dose-escalation (FDG-PET-CT)
Complete metabolic response rate on PET-CT scan will be reported at 3 months after treatment
Measured: 3 months
The loco-regional tumour control
Incidence of local or regional tumour recurrence rates will be presented.
Measured: 12 months
Disease-free survival
Disease-free survival rates (Kaplan-Meier estimates) will be presented at 3 and 12 months after completion of CRT.
Measured: 12 months
Overall survival
Overall survival rates (Kaplan-Meier estimates) will be presented at 3 and 12 months after completion of CRT.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2022
- Study start17 Jun 2022
- Primary completion16 Jun 2024 (estimated)
- Study completion16 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Guy's and St Thomas' NHS Foundation TrustThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Feasibility study
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Teresa Guerrero Urbano, Guy's and St Thomas' NHS Foundation Trust
- Investigators
- Teresa Guerrero Urbano, Principal investigator, Guy's and St Thomas' NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05393297
- Sponsor's protocol ID
- 22/LO/0056
- Other IDs
- 257601
- Acronym
- InGReS
- Status last verified
- Sep 2023
- First submitted
- 18 May 2022
- Last updated
- 13 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- InGReS: Intra-treatment Image Guided Adaptive Radiotherapy Dose-escalation Study
- ClinicalTrials.gov ID
- NCT05393297
- Acronym / sponsor ID
- InGReS / 22/LO/0056
- Conditions
- Head and Neck Cancer
- Keywords
- Radiotherapy, Adaptive, Dose-escalation, Oropharyngeal Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Study start
- 17 Jun 2022 (actual)
- Primary completion
- 16 Jun 2024 (estimated)
- Study completion
- 16 Jun 2025 (estimated)
- First posted
- 26 May 2022 (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.
InGReS is a phase I pilot study of adaptive dose-escalated radiotherapy in combination with platinum-based chemotherapy (CRT) for locally advanced head and neck cancer.
InGReS will assess the feasibility of adapting the radiotherapy (RT) plan for each patient, based on anatomical and metabolic changes in the tumour seen on MRI and FDG-PET-CT performed after 2 weeks of CRT in a multicentre setting. The overall aim of the trial is to determine the safety and feasibility of delivering dose-escalated Intensity Modulated Radiotherapy (IMRT) to the residual primary tumour, as seen on intra-treatment imaging, in the final 3 weeks of RT.
Detailed description
The study will recruit 15 patients with locally advanced oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) who are suitable for primary treatment with concurrent chemo-radiation. The main aim is to see whether it is feasible to perform a FDG positron emission tomography-computed tomography (FDG-PET-CT) and Magnetic Resonance Imaging (MRI) scan after 2 weeks of radiotherapy and re-plan the radiotherapy to escalate the dose of radiotherapy delivered to the residual primary tumour as seen on PET-CT and MRI.
Patients will commence with standard chemo-radiotherapy; 70 Gray (Gy) in 35 fractions with concomitant platinum chemotherapy. After 2 weeks of chemo-radiotherapy patients will have an intra-treatment FDG-PET-CT and MRI scan to assess early response to treatment. Patients with evidence of residual disease will proceed with the dose-escalation phase of the study, with an adaptive radiotherapy re-plan and dose-escalation to the residual primary tumour.
The study will establish acute and late radiotherapy toxicity rates in patients who receive dose-escalated RT, particularly the effect of treatment on long-term swallowing function. The study hypothesis is that mucosal toxicity rates for dose-escalated treatment will be equivalent to those for standard CRT, according to published data. Furthermore, it will also explore whether changes in FDG-PET-CT and MRI during treatment correlate with patient outcomes and potential blood-based biomarkers of treatment response. Local control, disease-free and overall survival will be assessed for both standard and dose-escalated approaches.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Feasibility study
| Arm | Type | Receives |
|---|---|---|
| HNSCC receiving (chemo)radiotherapy | Experimental | Diagnostic Test: Imaging: Intra-treatment FDG-PET-CT and MRI, Radiation: Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalationRadiation: Intra-treatment FDG-PET-CT and MRI will be used to identify tumours and patients for dose-escalation. Patients identified for dose-escalation (boost) will undergo adaptive radiotherapy replanning, with the primary tumour (GTVp) receiving 76.9Gy in 35 fractions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Locally advanced, histologically confirmed squamous cell carcinoma (SCC) of the oropharynx and hypopharynx to be treated with primary radical chemo-radiotherapy:
- ≥T2 tumours:
- Staging MRI showing minimum diameter of primary tumour greater than or equal to 1cm
- Staging 18F-FDG-PET/CT showing adequate uptake in the primary tumour, defined as SUVmax of ≥ 5.0
- Multidisciplinary team (MDT) decision to treat with primary CRT with curative intent
Key exclusion criteria (7 listed)
- Previous radiotherapy to the head and neck region interfering with the protocol treatment plan
- Patients requiring neo-adjuvant chemotherapy
- Inability to tolerate PET or MRI; general contra-indications to MRI
- Contra-indication to gadolinium
- Baseline SUVmax < 5.0 in the primary tumour on PET-CT or smaller than 1cm in axial dimensions on cross sectional imaging
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 |
|---|---|---|
| Imaging: Intra-treatment FDG-PET-CT and MRIFDG-PET-CT and MRI scan will be used during radiotherapy to assess early treatment response and identify tumours eligible for dose-escalation. | Diagnostic test | HNSCC receiving (chemo)radiotherapy |
| Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalationTumours eligible for dose-escalation (boost), as seen on intra-treatment FDG-PET-CT and MRI scan, will receive 76.9 Gy to the residual gross primary tumour. The radiotherapy plan will be replanned to incorporate the simultaneous-integrated-boost to the GTVp which will be delivered over the last 3 weeks of treatment | Radiation | HNSCC receiving (chemo)radiotherapy |
Primary outcome
To assess the safety of delivering an additional 10% dose (biological rather than numerical) of radiotherapy to the residual primary tumour during radiotherapy
Time frame: 12 months
Incidence of grade 3 or above late Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC) mucosal toxicity or feeding tube retention rate following completion of treatment. An excess rate of >14% would be regarded as unacceptable.
13 secondary outcomes
Incidence of grade 4 acute mucosal toxicity (NCI CTCAE)
Time frame: 12 weeks
Incidence of grade 3 or above late non-mucosal toxicity (NCI CTCAE)
Time frame: 12 months
Incidence of grade 3 or above late non-mucosal toxicity (RTOG/EORTC)
Time frame: 12 months
Incidence of grade 3 or above late non-mucosal toxicity (LENT/SOMA criteria)
Time frame: 12 months
To assess swallowing panel measurements including qualitative swallowing assessments (MDADI)
Time frame: 12 months
To assess patient reported outcomes measures and quality of life questionnaires (UW-QOL v 4.1)
Time frame: 12 months
To assess patient reported outcomes measures and quality of life questionnaires (EORTC QLQ-C30 and EORTC QLQ-H&N43)
Time frame: 12 months
To assess results of quantitative swallowing assessments (Videofluoroscopy)
Time frame: 12 months
To assess late toxicity rates and the effect of treatment on swallowing function (100ml water swallow)
Time frame: 12 months
To assess tumour response to adaptive radiotherapy dose-escalation (FDG-PET-CT)
Time frame: 3 months
The loco-regional tumour control
Time frame: 12 months
Disease-free survival
Time frame: 12 months
Overall survival
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Individual participant dataSharing planned: No
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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.
Teresa Guerrero Urbano principal investigator
Guy's and St Thomas' NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Imaging: Intra-treatment FDG-PET-CT and MRI and Intra-treatment Image-Guided Adaptive Radiotherapy Dose-escalation in people with Head and Neck Cancer, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
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 9 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 13 Sep 2023. 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 United Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Smruti Gorsia (+44 (0)20 7188 2018, HeadandNeckResearchTeam@gstt.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety of delivering an additional 10% dose (biological rather than numerical) of radiotherapy to the residual primary tumour during radiotherapy (time frame: 12 months). 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 13 Sep 2023.