Early Response Evaluation of Proton Therapy by PET-imaging in Squamous Cell Carcinoma Located in the Head and Neck

NCT03513042 | Terminated DMC

• 3 other identifiers: NL63825.058.17916.18.008P17.291
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

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

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years after start of IMPT

Secondary Outcomes (4)

• 3-year overall survival

  3 years after start of IMPT

• 3-year disease-specific survival

  3 years after start of IMPT

• 3-year disease-free survival

  3 years after start of IMPT

• tumour response per RECIST

  3 years after start of IMPT

Study Arms (1)

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.

Radiation: Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy

Interventions

Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy RADIATION

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)

Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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);
• 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;

Sponsors & Collaborators

• Leiden University Medical Center: lead
• HollandPTC: collaborator

Study Sites (1)

Holland Proton Therapy Centre (HollandPTC)

Delft, South Holland, 2629 JH, Netherlands

Location

Related Links

• Holland Proton Therapy Centre (HollandPTC)

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Hypoxia; Head and Neck Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Dennis Vriens, MD, PhD

  Leiden University Medical Center (LUMC)

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dennis Vriens, MD, PhD (Study Coordinator)

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: May 1, 2018
• Study Start: January 21, 2021
• Primary Completion: November 23, 2022
• Study Completion: November 23, 2022
• Last Updated: December 6, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: to be determined
• Access Criteria: to be determined

Locations

NL (1)