E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and neck squamous cell carcinoma (HNSCC) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate FAZA-PET/CT as a prognostic factor of the loco-regional control rate at 2 years in HNSCC patients receiving chemo-radiotherapy ± nimorazole.
- Time to locoregional recurrence is counted from the day of randomization to the day of the first record of local or regional progression. Distant recurrence, second cancer and death in absence of locoregional recurrence are not considered events of interest. The follow-up will be done regularly according to a well-defined agenda.
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E.2.2 | Secondary objectives of the trial |
- To evaluate the change in FAZA uptake at day 14 (14 days after starting chemo-radiotherapy treatment relative to baseline), against patient’s outcome measured by loco-regional control rate at 2 years.
- To investigate the agreement between FAZA uptake and 15 gene signatures.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients randomized in any of the two arms of EORTC 1219 trial
- No contraindication to FAZA-PET/CT: pregnant or breast-feeding woman; for woman subject of childbearing potential, a pregnancy test will be done within 72 hours before the examination.
- No contraindication to contrast MRI:
= Pregnant woman (pregnancy test will be done within 72 hours before exam)
= Patient with metallic implant as vascular clips, cochlear implants or metal foreign body
= Patient with cardiac pacemaker or implanted cardioverter-defibrillator
= Renal insufficiency (glomerular filtration rate GFR < 30ml/min)
- Patients must be scanned on a PET/CT scanner accredited, and in compliance with the provided imaging guidelines.
- Biopsy must be performed 2 weeks before imaging scans.
- Patient must have given written informed consent to participate to the imaging sub-study.
- Delay between the baseline scans (FAZA-PET/CT and multiparametric MRI) and the start of the radiotherapy < 7 days.
- Patients with at least one measurable lesion at baseline defined as a lesion larger than 2 cm in diameter. |
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E.4 | Principal exclusion criteria |
- All patient failing one or more of the inclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- To evaluate FAZA-PET/CT parameters as prognostic factors for the loco-regional control rate at 2 years in HNSCC patients receiving chemo-radiotherapy ± nimorazole.
- Time to locoregional recurrence is counted from the day of randomization to the day of the first record of local or regional progression. Distant recurrence, second cancer and death in absence of locoregional recurrence are not considered events of interest.
The PET / CT scans objective parameters for hypoxia will be determined within the primary tumor and the pathologic nodes, based on standardized uptake values (SUV), for example: SUVmax, SUVmean, total hypoxic volume x SUVmean.
Definition of hypoxia within a tumor on FAZA PET/CT:
A hypoxic voxel will be defined as a voxel expressing a SUV equal or above the SUVmean of the posterior contralateral neck muscles plus three standard deviations (Servagi-Vernat S, et al. A prospective clinical study of ¹⁸F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy. Eur J Nucl Med Mol Imaging. 2014 Aug;41(8):1544-52.).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and 2 weeks after start of radiotherapy. |
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E.5.2 | Secondary end point(s) |
- To evaluate the change in FAZA uptake at day 14 (14 days after starting chemo-radiotherapy treatment relative to baseline), against patient’s outcome measured by loco-regional control rate at 2 years.
- To investigate the agreement between FAZA uptake and 15 gene signatures.
Definition of response or non-response by repeated scans (pre-/during treatment):
In the patients with tumors having a hypoxic volume at baseline, a threshold of hypoxic volume change will be explored to define the response or non-response, based on patient outcomes (loco-regional control rate at year 2).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |