E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
local, regional or combined locoregional recurrence of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx in previously irradiated tissue, with former irradiation with curative intent. |
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E.1.1.1 | Medical condition in easily understood language |
recurrent head or neck cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 derive the maximum tolerated dose of hypofractionated stereotactic body radiotherapy (SBRT) using dose painting by numbers with immunomodulating systemic therapy in patients that are reirradiated for recurrent squamous cell carcinoma of the head and neck. |
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E.2.2 | Secondary objectives of the trial |
To assess symptom palliation To assess local control. To estimate overall and progression-free survival. To estimate grade ≥ 3 toxicity-free survival To assess quality-of-life (QOL) To assess the topographic distribution of recurrence (inside/outside FDG-avid GTV) To assess time to further treatment To assess the immune response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically confirmed local, regional or combined locoregional recurrence of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx or cancer of unknown primary (CUP) in the neck in previously irradiated tissue, with former irradiation with curative intent. Patients with non-symptomatic distant metastases and local, regional or combined locoregional recurrence can be included. In case of non-metastatic disease, the recurrence must be primarily unresectable recurrence and/or patients refused surgery. Time interval 6-24 months after the end of the initial radio(chemo)therapy for primary head and neck cancer. Decision of the Head and Neck Tumor Boards at the recruiting centre to offer salvage radio(chemo)therapy, palliative chemotherapy or anti-PD-1 antibody treatment with nivolumab for cisplatin-refractory locoregional recurrent head and neck squamous cell carcinoma. Karnofsky performance status ≥ 70. Age ≥ 18 years old. Informed consent obtained, signed and dated before specific protocol procedures.
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E.4 | Principal exclusion criteria |
Previous radiotherapy was for cT1-2 cN0 M0 glottic cancer. • Grade ≥ 4 late toxicity after the initial radio(chemo)therapy. Brachytherapy as treatment for second primary / recurrence. Previous (combination with) immunotherapy for the primary or the recurrent squamous cell carcinoma. Impossibility of oral intake of cylophosphamide. For patients receiving cyclophosphamide: Necessary intake during therapy of allopurinol, amiodarone, digoxin, hydrochlorothiazide, indomethacin, phenobarbital, phenytoin, warfarin. clopidogrel, ticlopidine, carbamazepine, efavirenz, rifampicine, ritonavir High risk for arterial blow-out: 1 of following criteria is sufficient to exclude patients: o (1) soft tissue necrosis o (2) skin invasion of the recurrent cancer o (3) circumferential involvement of > 180° of a carotid artery) Symptomatic distant metastases. Other uncontrolled second primary tumors. Pregnant or lactating women. Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study. Patient unlikely to comply with protocol, i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety, defined as absence of grade ≥ 4 acute or subacute toxicity until 3 months after treatment and absence of grade ≥ 3 mucosal ulceration or any other kind of grade ≥ 3 toxicity > 3 months after treatment). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months after treatment and end of follow up |
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E.5.2 | Secondary end point(s) |
Toxicity scoring (CTCAE version …) Local control Overall and disease-free survival QOL topographic distribution of recurrence (inside/outside FDG-avid GTV) time to further treatment the immune response |
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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 | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |