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Early Response Evaluation of Proton Therapy by PET-imaging in Squamous Cell Carcinoma Located in the Head and Neck (ERM-PT-HNSCC)

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ClinicalTrials.gov Identifier: NCT03513042
Recruitment Status : Not yet recruiting
First Posted : May 1, 2018
Last Update Posted : May 2, 2018
Sponsor:
Collaborator:
Holland Particle Therapy Centre (HollandPTC)
Information provided by (Responsible Party):
Dennis Vriens, MD, PhD, Leiden University Medical Center

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.


Condition or disease Intervention/treatment
Squamous Cell Carcinoma of the Head and Neck Radiation: Intensity Modulated Proton Therapy (IMPT) +/- Chemotherapy

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Early Response Evaluation of Proton Therapy by PET-imaging in Squamous Cell Carcinoma Located in the Head and Neck
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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

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)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 3-year overall survival [ Time Frame: 3 years after start of IMPT ]
    similar to LRFS but 'death from any cause' will be the event of interest

  2. 3-year disease-specific survival [ Time Frame: 3 years after start of IMPT ]
    similar to LRFS but 'death from HNSCC' will be the event of interest

  3. 3-year disease-free survival [ Time Frame: 3 years after start of IMPT ]
    similar to LRFS but 'any recurrence (including systemic)' will be the event of interest

  4. tumour response per RECIST [ Time Frame: 3 years after start of IMPT ]
    Response Evaluation Criteria In Solid Tumours (RECIST v1.1) tumour response during structured radiological follow-up



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

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;
  • due to the relation between HPV/p16-status and prognosis, treatment response and the experience that HPV/p16-positive patients seem more eager to participate in studies, inclusion of patients with known positive HPV/p16-status will be limited to 50% of included subjects (population prevalence: 25-60%) [66, 67];
  • has provided legal informed consent according to ICH/GCP and national/local regulations.

Exclusion Criteria:

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;
  • had previous surgical resection for the same disease;
  • had any prior radiotherapy to the head and neck region within the last 3 years ;
  • 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 PI 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 14 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03513042


Contacts
Contact: Dennis Vriens, MD, PhD +31715297709 D.Vriens@lumc.nl

Sponsors and Collaborators
Leiden University Medical Center
Holland Particle Therapy Centre (HollandPTC)
Investigators
Study Chair: Dennis Vriens, MD, PhD Leiden University Medical Center (LUMC)

Additional Information:
Responsible Party: Dennis Vriens, MD, PhD, Dennis Vriens, MD, PhD (Study Coordinator), Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT03513042     History of Changes
Other Study ID Numbers: NL63825.058.17
916.18.008 ( Other Grant/Funding Number: The Netherlands Organisation for Health R&D (ZonMW) )
P17.291 ( Other Identifier: MREC LUMC )
First Posted: May 1, 2018    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: raw data will be made publicly available as required by the funding body. A datamanagement plan including public sharing is available on request.
Time Frame: to be determined
Access Criteria: to be determined

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dennis Vriens, MD, PhD, Leiden University Medical Center:
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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site