Clinical trial NCT05393297: InGReS: Intra-treatment Image Guided Adaptive Radiotherapy Dose-escalation Study
Official title: InGReS: Intra-treatment Image Guided Adaptive Radiotherapy Dose-escalation Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Head and Neck Cancer
Keywords: Radiotherapy
Adaptive
Dose-escalation
Oropharyngeal Squamous Cell Carcinoma
Hypopharyngeal Squamous Cell Carcinoma
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2022-05-26
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Feasibility study
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: Inclusion criteria:

1. Locally advanced, histologically confirmed squamous cell carcinoma (SCC) of the oropharynx and hypopharynx to be treated with primary radical chemo-radiotherapy:

   1. Hypopharyngeal cancer - HPV negative OR HPV positive
   2. 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)
2. ≥T2 tumours:
3. Staging MRI showing minimum diameter of primary tumour greater than or equal to 1cm
4. Staging 18F-FDG-PET/CT showing adequate uptake in the primary tumour, defined as SUVmax of ≥ 5.0
5. Multidisciplinary team (MDT) decision to treat with primary CRT with curative intent
6. Patients fit for radical treatment with primary CRT
7. WHO Performance Status 0-1

Exclusion criteria:

1. Previous radiotherapy to the head and neck region interfering with the protocol treatment plan
2. Patients requiring neo-adjuvant chemotherapy
3. Inability to tolerate PET or MRI; general contra-indications to MRI
4. Contra-indication to gadolinium
5. Baseline SUVmax \< 5.0 in the primary tumour on PET-CT or smaller than 1cm in axial dimensions on cross sectional imaging
6. GFR \<40ml/min
7. 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).

Primary outcomes:
measure: To assess the safety of delivering an additional 10% dose (biological rather than numerical) of radiotherapy to the residual primary tumour during radiotherapy
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of grade 4 acute mucosal toxicity (NCI CTCAE)
timeFrame: 12 weeks
measure: Incidence of grade 3 or above late non-mucosal toxicity (NCI CTCAE)
timeFrame: 12 months
measure: Incidence of grade 3 or above late non-mucosal toxicity (RTOG/EORTC)
timeFrame: 12 months
measure: Incidence of grade 3 or above late non-mucosal toxicity (LENT/SOMA criteria)
timeFrame: 12 months
measure: To assess swallowing panel measurements including qualitative swallowing assessments (MDADI)
timeFrame: 12 months
measure: To assess patient reported outcomes measures and quality of life questionnaires (UW-QOL v 4.1)
timeFrame: 12 months
measure: To assess patient reported outcomes measures and quality of life questionnaires (EORTC QLQ-C30 and EORTC QLQ-H&N43)
timeFrame: 12 months
measure: To assess results of quantitative swallowing assessments (Videofluoroscopy)
timeFrame: 12 months
measure: To assess late toxicity rates and the effect of treatment on swallowing function (100ml water swallow)
timeFrame: 12 months
measure: To assess tumour response to adaptive radiotherapy dose-escalation (FDG-PET-CT)
timeFrame: 3 months
measure: The loco-regional tumour control
timeFrame: 12 months
measure: Disease-free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Teresa Guerrero Urbano
role: PRINCIPAL_INVESTIGATOR
References: