E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
in patients with platinum-resistant head and neck squamous cell carcinoma after relapse to immunotherapy “ |
in pazienti affetti da carcinoma squamoso del distretto testa-collo, platino resistenti in progressione ad immunoterapia |
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E.1.1.1 | Medical condition in easily understood language |
in patients with platinum-resistant head and neck squamous cell carcinoma after relapse to immunotherapy “ |
in pazienti affetti da carcinoma squamoso del distretto testa-collo, platino resistenti in progressione ad immunoterapia |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028997 |
E.1.2 | Term | Neoplasm malignant |
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 the activity of tepotinib in combination with cetuximab in terms of tumor response |
Valutare l’attività di tepotinib + cetuximab |
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E.2.2 | Secondary objectives of the trial |
To further evaluate the activity of the combination of tepotinib and cetuximab in terms of: * duration of response (DoR) and disease control rate (DCR) * progression-free survival (PFS) * overall survival (OS) To evaluate the safety and tolerability of tepotinib in combination with cetuximab Impact on Quality of Life (QoL) |
Valutazioni aggiuntive sull’attività di tepotinib + cetuximab in termini di: * duration of response (DoR) e disease control rate (DCR) * progression-free survival (PFS) * overall survival (OS) Valutare la tolleranza di tepotinib + cetuximab Impatto sulla Quality of Life (QoL) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adults > 18 years old - Patients must have histologically confirmed HNSCC from any primary site; nasopharyngeal carcinoma and paranasal sinus, will be included; squamous cell carcinoma of unknown primary, clearly related to the head and neck, will be included - Recurrent/metastatic disease, fulfilling at least one of the criteria defined below: a) Incurable disease as assessed by surgical or radiation oncology b) Metastatic (M1) disease c) Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible - For patients with oropharyngeal primary site or unknown primary site only: tumoral human papillomavirus (HPV) status must be negative, as established; acceptable standards include p16 immunohistochemistry (where a tumor is classified as p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or assessment of HPV deoxyribonucleic acid (DNA) For patients with nasopharyngeal cancer only or unknown primary site only: tumoral Epstein- Barr Virus (EBV) status must be negative. |
- Adulti > 18 anni - I pazienti devono avere HNSCC confermato istologicamente da qualsiasi sito primario; saranno inclusi carcinoma nasofaringeo e seno paranasale; Sarà incluso il carcinoma a cellule squamose di origine sconosciuta, chiaramente correlato alla testa e al collo. - Malattia ricorrente/metastatica, che soddisfi almeno uno dei criteri definiti di seguito: a) Malattia incurabile valutata mediante oncologia chirurgica o radiologica b) Malattia metastatica (M1) c) malattia persistente o progressiva a seguito di radiazioni curative e non candidata per il salvataggio chirurgico a causa di incurabilità o morbilità; I pazienti che rifiutano la chirurgia radicale sono eleggibili - Per i pazienti con sito primario orofaringeo o solo sito primario sconosciuto: lo stato del papillomavirus umano tumorale (HPV) deve essere negativo, come stabilito; Gli standard accettabili includono l'immunoistochimica p16 (dove un tumore è classificato come p16-positivo quando mostra colorazione nucleare e citoplasmatica diffusa in almeno il 70% delle cellule tumorali) e/o valutazione dell'acido desossiribonucleico (DNA) HPV) Per i pazienti con solo carcinoma nasofaringeo o solo sito primario sconosciuto: lo stato del virus di Epstein-Barr (EBV) tumorale deve essere negativo. |
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E.4 | Principal exclusion criteria |
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent; - Prior treatment with a hepatocyte growth factor (HGF)/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or ARQ197; - Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 2 weeks (radiotherapy or surgery); - Failure to recover to grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental therapy, with the exception of: alopecia, grade =< 2 peripheral neuropathy, grade =< 2 cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values detailed below), hypokalemia (acceptable values detailed below), and the acceptable hematologic values summarized above; a washout period of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug is required; - Previous treatment with cetuximab for RM disease. Use of cetuximab is allowed if given concurrently with radiation; - Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis; - Peripheral edema >= grade 2 per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; |
- Anamnesi di gravi reazioni allergiche o anafilattiche o ipersensibilità alle proteine ricombinanti o agli eccipienti nell'agente sperimentale; - Trattamento precedente con un fattore di crescita degli epatociti (HGF)/inibitore cMet come rilotumumab, crizotinib, MetMAb o ARQ197; -Le metastasi incontrollate del sistema nervoso centrale (SNC), comprese le metastasi leptomeningee, non sono consentite; I soggetti con metastasi cerebrali precedentemente trattate saranno ammessi se le metastasi cerebrali sono rimaste stabili senza trattamento steroideo per almeno 2 settimane (radioterapia o chirurgia) -Mancato recupero al grado 1 o basale da tutti gli effetti tossici di precedenti chemioterapia, radioterapia, terapia biologica, immunoterapia e/o terapia sperimentale, ad eccezione di: alopecia, grado = < 2 neuropatia periferica, grado = < 2 eruzione cutanea correlata a cetuximab o altri cambiamenti cutanei, ipomagnesemia (valori accettabili dettagliati di seguito), ipokaliemia;(valori accettabili dettagliati di seguito) e i valori ematologici accettabili riassunti sopra; è richiesto un periodo di washout di 3 settimane da qualsiasi precedente chemioterapia citotossica, terapia mirata, immunoterapia o farmaco sperimentale; -Precedente trattamento con cetuximab per la malattia di RM. L'uso di cetuximab è consentito se somministrato in concomitanza con le radiazioni; - Malattia polmonare significativa, inclusa ipertensione polmonare o polmonite interstiziale; - Edema periferico >= grado 2 per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) versione 5.0; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response (OR, confirmed complete response [CR] or partial response [PR]) determined according to RECIST Version 1.1 assessed by the Investigators |
Risposta obiettiva (OR, risposta completa confermata [CR] o risposta parziale [PR]) determinata secondo RECIST Versione 1.1 valutata dagli sperimentatori |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Complete Response (CR) defined as at least two determinations of CR at least 4 weeks apart (with no PD in between) Partial Response (PR) defined as at least two determinations of PR or better (PRfollowed by PR or PR followed by CR) at least 4 weeks apart (and not qualifying for a CR), with no PD in between Stable Disease (SD) defined as at least one SD assessment (or better)[= 6 weeks] after start date (and not qualifying for confirmed CR or PR. Non-CR/non-PD (applicable only to participants with non- measurable disease at Baseline) = at least one non-CR/non-PD assessment (or better) [= 6 weeks] afterstart date (and not qualifying for CR or PR). PD = PD = 12 weeks after start date (and not qualifying for CR, PR, |
Risposta completa (CR) definita come almeno due determinazioni di CR a distanza di almeno 4 settimane (senza PD in mezzo) Risposta parziale (PR) definita come almeno due determinazioni di PR o migliore (PR seguita da PR o PR seguita da CR) a distanza di almeno 4 settimane (e non qualificanti per una CR), senza PD in mezzo Malattia stabile (DS) definita come almeno una valutazione SD (o migliore) [= 6 settimane] dopo la data di inizio (e non qualificante per CR o PR confermate. Non CR/non PD (applicabile solo ai partecipanti con malattia non misurabile al basale) = almeno una valutazione non CR/non PD (o migliore) [= 6 settimane] dopo la data di inizio (e non idoneo per CR o PR). PD = PD = 12 settimane dopo la data di inizio (e non qualificanti per CR, PR, |
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E.5.2 | Secondary end point(s) |
DoR and DCR according to RECIST 1.1 as assessed by the Investigators. ° PFS ° OS; To evaluate the safety and tolerability of tepotinib incombination with cetuximab; Impact on Quality of Life (QoL) |
DoR e DCR secondo RECIST 1.1 come valutato dagli sperimentatori. ° PFS ° OS; To evaluate the safety and tolerability of tepotinib incombination with cetuximab; Impact on Quality of Life (QoL) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3, 6, 9, 12,15, and 18 months; every time; Pre- study (within 2 weeks of study registration) and Week 9, Cycle 3 of Intervention] |
3, 6, 9, 12,15, 18 mesi; in qualsiasi momento; Pre- study (within 2 weeks of study registration) and Week 9, Cycle 3 of Intervention] |
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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 | No |
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 | No |
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 | 10 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |