E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
recurrent or metastatic cervical cancer |
cáncer cervical recurrente o metastásico |
|
E.1.1.1 | Medical condition in easily understood language |
recurrent or metastatic cervical cancer |
cáncer cervical recurrente o metastásico |
|
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 | 20.0 |
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) |
|
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 |
• Determine the anti-tumor efficacy in patients with cervical cancer |
• Determinar la eficacia antitumoral en pacientes con cáncer de cuello de útero |
|
E.2.2 | Secondary objectives of the trial |
• Evaluate durability • Evaluate other clinical outcomes • Assess safety and tolerability |
• Evaluar la durabilidad. • Evaluar otros resultados clínicos. • Evaluar la seguridad y la tolerabilidad. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with extra-pelvic metastatic or recurrent cervical cancer including squamous cell, adenocarcinoma or adenosquamous histology, that: 1. Have experienced disease progression during or after treatment with: - Paclitaxel+cisplatin or carboplatin OR - Paclitaxel+topotecan, in combination with bevacizumab unless patients are ineligible for bevacizumab treatment according to local standards. 2. Have received no more than 2 prior systemic treatment regimens for recurrent or metastatic cervical cancer. Chemotherapy administered in combination with radiation therapy is not considered a prior systemic regimen. 3. Are not candidates for curative therapy, including but not limited to, radiotherapy or exenterative surgery. • Age ≥ 18 years • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 • Life expectancy of at least three months • A negative serum pregnancy test for patients of reproductive potential • Patients of reproductive potential must agree to use adequate contraception during and for 6 months after the last IMP administration • Following receipt of verbal and written information about the trial, patients must provide signed informed consent before any trial-related activity is carried out • Acceptable coagulation status: o International normalized ratio (INR) ≤ 1.2 (without anti-coagulation therapy). o Activated partial thromboplastin time (aPTT) ≤ 1.25 ULN. o Patients on anti-coagulation therapy (e.g., warfarin) must be on a steady dose (no active titration) for at least 4 weeks prior to screening and must have an INR ≤ 2.5 for eligibility. Concurrent use of prophylactic AcetylSalicylic Acid (ASA, e.g., aspirin) for patients on anti-coagulation therapy (e.g., warfarin) is prohibited. |
• Pacientes con cáncer de cuello de útero metastásico o recurrente extrapélvico con histología de células escamosas, adenocarcinoma o adenoescamoso, que: o Hayan experimentado progresión de la enfermedad durante o después del tratamiento con: - Paclitaxel + cisplatino o carboplatino O - Paclitaxel + topotecán, en combinación con bevacizumab, a menos que las pacientes no sean aptas para el tratamiento con bevacizumab de conformidad con los estándares locales.
o No hayan recibido anteriormente más de 2 pautas posológicas sistémicas para cáncer de cuello de útero recurrente o metastásico. La quimioterapia administrada en combinación con radioterapia no se considera una pauta sistémica previa o No sean candidatas para un tratamiento curativo, incluidas, entre otras, la radioterapia o la cirugía de evisceración.
• Edad ≥18 años. • Estado general 0 o 1 del ECOG (Eastern Cooperative Oncology Group • Esperanza de vida de, al menos, tres meses. • Prueba de embarazo en suero negativa para las pacientes con capacidad reproductiva • • Las pacientes con capacidad reproductiva deberán aceptar utilizar métodos anticonceptivos adecuados durante el ensayo y durante los 6 meses posteriores a la administración de la última dosis del PEI. • Tras haber recibido toda la información oral y escrita sobre el ensayo, las pacientes deberán facilitar un consentimiento informado firmado antes de que se lleven a cabo las actividades relacionadas con el ensayo. • Estado de coagulación aceptable: o Índice Internacional Normalizado (INR) ≤1,2 (sin tratamiento anticoagulante). o Tiempo de tromboplastina parcial activada (TTPa) ≤1,25 LSN. A las pacientes que estén recibiendo un tratamiento anticoagulante (por ejemplo, con warfarina) se les administrará una dosis estable (sin ajuste de dosis activo) durante al menos las 4 semanas previas a la selección y deberán tener un INR ≤2,5 para ser consideradas aptas. Está prohibida la administración concurrente de ácido acetilsalicílico (ASA; aspirina, por ejemplo) profiláctico a las pacientes que estén recibiendo un tratamiento anticoagulante (por ejemplo, con warfarina). |
|
E.4 | Principal exclusion criteria |
• Known past or current coagulation defects • Ongoing major bleeding • Clinically significant cardiac disease • Other cancer: Known past or current malignancy other than inclusion diagnosis |
• Defectos conocidos de coagulación pasados o actuales • Sangrado mayor continuo • enfermedad cardíaca clínicamente significativa • Otro cáncer: malignidad pasada o presente conocida distinta del diagnóstico de inclusión |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Confirmed objective response rate based upon RECIST v1.1 assessed by the independent review committee |
• La tasa de respuesta objetiva (TRO) según los criterios RECIST v1.1, evaluada por el comité de revisión independiente (CRI). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
Durante el ensayo, ver el Protocolo |
|
E.5.2 | Secondary end point(s) |
• Duration of response (DOR) based upon RECIST v1.1 • Confirmed objective response rate based upon RECIST v1.1 assessed by the investigator • Time to response based upon RECIST v1.1 • Progression free survival based upon RECIST v1.1 • Overall survival • Adverse events and safety laboratory parameters • Pharmacokinetics (PK) • Immunogenicity |
• Duración de la respuesta (DR) según los criterios RECIST v1.1, • TRO confirmada según los criterios RECIST v1.1, evaluada por el investigador. • El tiempo hasta la respuesta (THR) según los criterios RECIST v1.1 Supervivencia sin progresión (SSP) según los criterios RECIST v1.1 Supervivencia general (SG). • Acontecimientos adversos y parámetros analíticos de la seguridad. • Farmacocinética (FC). • Inmunogenicidad |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• During the trial, see protocol |
Durante el ensayo, ver el Protocolo |
|
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) | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 33 |
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 | No |
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 |
Belgium |
Czech Republic |
Denmark |
Germany |
Italy |
Spain |
Sweden |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |