E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrent or stage IVB cervical cancer |
Carcinoma della cervice ricorrente o metastatico |
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E.1.1.1 | Medical condition in easily understood language |
cervical cancer |
Carcinoma della cervice |
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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 | 10008342 |
E.1.2 | Term | Cervix carcinoma |
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 |
Dose escalation: To establish the MTD and RP2D of tisotumab vedotin in combination in subjects with cervical cancer Dose expansion: Evaluate the antitumor activity of tisotumab vedotin monotherapy and in combination in subjects with cervical cancer |
Incremente della dose: Stabilire la MTD e la RP2D di tisotumab vedotin in combinazione in soggetti con carcinoma della cervice. Espansione della dose: Valutare l’attività antitumorale di tisotumab vedotin in monoterapia e in combinazione in soggetti con carcinoma della cervice |
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E.2.2 | Secondary objectives of the trial |
• Assess safety and tolerability of tisotumab vedotin monotherapy and in combination. • Evaluate anti tumor activity • Evaluate durability of response of tisotumab vedotin monotherapy and in combination. • Evaluate clinical efficacy with tisotumab vedotin monotherapy and in combination. • To evaluate the pharmacokinetics (PK) and immunogenicity of tisotumab vedotin monotherapy and in combination. |
• Valutare la sicurezza e tollerabilità di tisotumab vedotinin in monoterapia e in combinazione • Valutare l'attività antitumorale • Valutare la durata della risposta di tisotumab vedotinin in monoterapia e in combinazione • Valutare l’efficacia clinica con tisotumab vedotinin in monoterapia e in combinazione • Valutare la farmacocinetica (PK) e l’immunogenicità di tisotumab vedotinin in monoterapia e in combinazione |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after standard of care treatments or are ineligible or intolerant to standard of care for recurrent or stage IVB cervical cancer. (Arms A, B and C only). - Must have squamous, adenosquamous, or adenocarcinoma of the cervix and must not have received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D and E only). - Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after at least one but no more than two prior systemic therapies for recurrent or stage IVB cervical cancer (Arm F and G only). - Must have baseline measurable disease per RECIST v1.1 (all arms). - Must be at least 18 years of age on the day of signing informed consent (All Arms). - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (All Arms). - Is not pregnant, breastfeeding, or expecting to conceive children within the projected duration of the trial and for at least 6 months after the last trial treatment administration. A WOCBP must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration (all arms). - Must sign an informed consent form (ICF) indicating the trial subject understands the purpose of and procedures required for the trial and are willing to participate in the trial (All Arms). |
• Devono presentare carcinoma della cervice squamoso, adenosquamoso o adenocarcinoma della cervice e aver mostrato progressione durante o dopo i trattamenti di terapia standard o essere intolleranti o non idonei a ricevere trattamenti standard per il carcinoma della cervice ricorrente o allo stadio IVB (solo i Bracci A, B e C). • Devono presentare carcinoma della cervice squamoso, adenosquamoso o adenocarcinoma della cervice e non aver ricevuto una pregressa terapia sistemica per carcinoma della cervice ricorrente o allo stadio IVB (solo i Bracci D ed E). • Devono presentare carcinoma della cervice squamoso, adenosquamoso o adenocarcinoma della cervice e aver mostrato progressione durante o dopo almeno uno ma non più di due terapie sistemiche precedenti per il carcinoma della cervice ricorrente o allo stadio IVB (solo Bracci F e G). • Devono avere una malattia misurabile al basale in base a criteri RECIST v1.1 (Tutti i Bracci). • Devono avere almeno =18 anni di età nel giorno della firma del consenso informato (Tutti i Bracci). • Presentano uno stato prestazionale secondo l’Eastern Cooperative Oncology Group (ECOG [Gruppo cooperativo orientale di oncologia]) pari a 0 o 1 (Tutti i Bracci). • Non è in gravidanza, in allattamento e non ha in previsione il concepimento di figli nella durata prevista della sperimentazione e per almeno 6 mesi dall’ultima somministrazione del trattamento sperimentale. Una donna in età fertile (WOCBP) deve acconsentire all’uso di contraccezione adeguata durante e per 6 mesi dall’ultima somministrazione della dose del trattamento sperimentale (Tutti i Bracci). • Devono firmare un modulo di consenso informato (ICF) indicante che il soggetto della sperimentazione ha compreso lo scopo e le procedure richieste per la sperimentazione e che è disposto a partecipare alla stessa (Tutti i Bracci). |
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E.4 | Principal exclusion criteria |
- Has clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. (All Arms) - Has clinical signs or symptoms of gastrointestinal obstruction and requires parenteral hydration and/or nutrition. Post-operative obstructions within 4 weeks of abdominal surgery are permitted. (All Arms) - Has clinically significant bleeding issues or risks (All arms) - Prior history (within 3 months) or current evidence of hemoptysis (1/2 teaspoon or more) (Arm A only) - Recent (within 4 weeks of first dose of trial treatment) clinically significant gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arm A only) - Recent (within 4 weeks of first dose of trial treatment) evidence of wound healing complications that require medical intervention (Arm A only) - Has active ocular surface disease at baseline. Subjects with prior history of cicatricial conjunctivitis are ineligible (All Arms). - Clinically significant cardiac disease (All arms) - Requires anti-coagulation therapy (Arm A only) - Known history of thromboembolic events (Arm A only) |
• Presenta idronefrosi bilaterale clinicamente rilevante che non può essere alleviata mediante stent ureterali o drenaggio percutaneo (Tutti i Bracci). • Presenta sintomi o segni clinici di ostruzione gastrointestinale e necessità di idratazione e/o nutrizione parenterale. Le ostruzioni post-operatorie entro 4 settimane dalla chirurgia addominale sono consentite (Tutti i Bracci). • Presenta problemi o rischi emorragici clinicamente significativi (Tutti i Bracci) o anamnesi pregressa (entro 3 mesi) o evidenza attuale di emottisi (1/2 cucchiaino da tè o più) (solo Braccio A) o emorragia gastrointestinale o vaginale recente (entro 4 settimane dalla prima dose del trattamento sperimentale) clinicamente significativa che richiede trasfusione di PRBC (solo Braccio A); o evidenza recente di complicazioni nella cicatrizzazione delle ferite (entro 4 settimane dalla prima dose del trattamento sperimentale) che richiede l’intervento medico (solo Braccio A). • Presenta malattia della superficie oculare in fase attiva al basale. I soggetti con pregressa anamnesi di congiuntivite cicatriziale non sono idonei (Tutti i Bracci). • Problemi o rischi cardiovascolari (Tutti i Bracci) • Richiede una terapia anticoagulante. (solo Braccio A) • Presenta un’anamnesi nota di eventi tromboembolici (solo Braccio A). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose escalation: Incidences of DLTs, AEs, SAEs, infusion-related AEs, CTCAE grade = 3 AEs, and AEs related to trial treatment during the trial Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 |
Incremente della dose: Incidenze di DLT, EA, EA seri, EA correlati all’infusione, EA di grado =3 secondo i Criteri comuni di terminologia per gli eventi avversi (CTCAE) e EA correlati al trattamento sperimentale durante la sperimentazione Espansione della dose: Tasso di risposta obiettiva (ORR) secondo i criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
- Durante la sperimentazione, vedi il protocollo |
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E.5.2 | Secondary end point(s) |
• Adverse events (AEs) and evaluation of safety laboratory parameters. • Objective Response Rate (ORR) per RECIST v1.1 (only dose escalation) • Duration of Response (DOR) per RECIST v1.1. • Time to Response (TTR) per RECIST v1.1. • Progression free survival (PFS) per RECIST v1.1. • Overall Survival (OS) • PK-concentrations and anti-drug antibodies (ADA) associated with tisotumab vedotin in combination.
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• Eventi avversi (EA) e parametri di laboratorio di sicurezza • Tasso di risposta obiettiva (ORR) in base ai criteri RECIST v1.1 • Durata della risposta (DOR) in base ai criteri RECIST v1.1 • Tempo alla risposta (TTR) in base ai criteri RECIST v1.1 • Sopravvivenza libera da progressione (PFS) in base ai criteri RECIST v1.1 • Sopravvivenza complessiva (OS) • Concentrazioni di PK e anticorpi anti-farmaco (ADA) associati a tisotumab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
Durante la sperimentazione, vedi il protocollo |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1b (dose escalation - dose expansion) |
Fase Ib (incremento della dose - espansione della dose) |
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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 | 7 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Turkey |
United States |
Belgium |
Czechia |
Denmark |
Germany |
Ireland |
Italy |
Netherlands |
United Kingdom |
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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
|
The trial is considered completed four years after the last subject is enrolled |
La sperimentazione è considerata conclusa quattro anni dopo l'arruolamento dell'ultimo paziente. |
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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 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |