E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-risk locally advanced carcinoma of the cervix (HRLACC) following concurrent chemotherapy and radiation therapy. |
Carcinoma del cuello del útero avanzado localmente de alto riesgo (HRLACC, por su sigla en inglés) después de la terapia de radiación y quimioterapia simultáneas. |
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E.1.1.1 | Medical condition in easily understood language |
HIGH RISK LOCALLY ADVANCED CERVICAL CANCER |
Cáncer de cuello uterino localmente avanzado de riesgo alto |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008231 |
E.1.2 | Term | Cervical cancer recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008236 |
E.1.2 | Term | Cervical cancer stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008235 |
E.1.2 | Term | Cervical cancer stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008234 |
E.1.2 | Term | Cervical cancer stage II |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008233 |
E.1.2 | Term | Cervical cancer stage I |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the disease free survival (DFS) of ADXS11-001 to placebo administered in the adjuvant setting following concurrent chemotherapy and radiotherapy (CCRT) administered with curative intent to subjects with high-risk locally advanced squamous, adenosquamous, or adenocarcinoma of the cervix (HRLACC). |
Comparar la supervivencia libre de enfermedad (DFS, por sus siglas en inglés) de ADXS11-001 administrado como adyuvante respecto a placebo después de la quimioterapia y radioterapia concurrentes (CCRT) administrados con intención curativa a pacientes con cáncer de cuello uterino (escamoso, adenoescamoso o adenocarcinoma) avanzado localmente de alto riesgo (HRLACC, por sus siglas en inglés). |
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E.2.2 | Secondary objectives of the trial |
To determine and compare the frequency and severity of adverse events (AEs) as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for the regimens administered on this study.
To evaluate the overall survival (OS) of ADXS11-001 administered in the adjuvant setting following definitive therapy of CCRT in subjects with HRLACC. |
Determinar y comparar la frecuencia y la gravedad de los eventos adversos (EA) para los regímenes administrados en este estudio, evaluados por los Criterios de Terminología Comunes para Eventos Adversos (CTCAE) del National Cancer Institute (NCA) versión 4.03.
Evaluar la supervivencia global (OS, según sus siglas en inglés) de ADXS11-001 administrado como adyuvante después de la terapia definitiva de quimiorradioterapia (CCRT por sus siglas en inglés), en pacientes con HRLACC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with: o Histological diagnosis of squamous cell, adenocarcinoma or adenosquamous carcinoma of the cervix who have undergone definitive therapy with a curative intent*
Subjects may have: o Stage IB2, IIA2, IIB with any of the following pelvic lymph node metastases criteria: -Biopsy proven pelvic node(s) -2 or more positive nodes by MRI/CT ≥1.5 cm shortest dimension -2 or more positive pelvic nodes by PET with standard uptake value ≥2.5 OR o All Stage IIIA, IIIB, IVA OR o Any FIGO stage with para-aortic lymph node metastases criteria (defined by 1 of the following): - Biopsy proven para-aortic node(s) - 1 or more positive para-aortic node(s) by MRI/CT >1.5 cm shortest dimension - 1 or more positive para-aortic node(s) by PET with SUV >2.5
Subjects must have received definitive therapy with curative intent, which consist of at least 4 weeks treatment with cisplatin and a minimum of 40 Gy external beam radiation therapy (EBRT). NOTE: Brachytherapy is permitted.
Subjects must be: o Age 18 years or older o GOG performance status 0 – 1 o ANC ≥1000 x 109/L o Platelets ≥75 x 109/L o Bilirubin ≤1.5 x ULN o AST or ALT ≤2.5 x ULN o Serum creatinine or measured creatinine clearance ≤1.5 x ULN o Toxicities resulting from definitive therapy must resolve to ≤Grade 1 prior to randomization, with the exception of peripheral neuropathy (sensory and motor) which must resolve to ≤Grade 2. |
• Pacientes con: o Diagnóstico histológico de células escamosas, adenocarcinoma o carcinoma adenoescamoso de cuello de útero, que se hayan sometido a terapia definitiva con intención curativa*
• Las pacientes pueden tener: o Estadios IB2, IIA2, IIB con cualquiera de los siguientes criterios de metástasis de ganglios linfáticos pélvicos: + Ganglio(s) en la pelvis confirmados mediante biopsia + 2 ganglios positivos o más según resonancia magnética (IRM)/ tomografía computada (TC) con ≥1.5 cm en su dimensión más corta + 2 ganglios pélvicos positivos o más según tomografía por emisión de positrones (TEP) con valor de absorción estándar (SUV, por su sigla en inglés) de ≥2.5 O o Todas los estadios IIIA, IIIB, IVA O o Cualquier estadio FIGO con criterios de metástasis de ganglios linfáticos paraaórticos (definido por 1 de los siguientes): + Ganglio(s) paraaórtico(s) confirmado(s) mediante biopsia + 1 o más ganglios paraaórticos positivos segúnIRM/TC, con >1.5 cm en su dimensión más corta + 1 o más ganglios paraaórticos positivos según TEPcon SUV >2.5 Las pacientes tienen que haber recibido terapia definitiva con intención curativa, la cual consiste de al menos 4 semanas de tratamiento con cisplatino y un mínimo de 40 Gy de radioterapia con rayos externos (EBRT, por sus siglas en inglés). NOTA: Se permite la braquiterapia.
• Las pacientes deben tener: o 18 años de edad o más o estado funcional de GOG 0 – 1 o ANC ≥1000 x 109/l o Plaquetas ≥75 x 109/l o Bilirrubina ≤1.5 x ULN o AST o ALT ≤2.5 x ULN o Creatinina en suero o aclaramiento de la creatinina medido ≤1.5 x ULN o Las toxicidades que resulten de la terapia definitiva deben resultar de ≤Grado 1 antes de la aleatorización, con excepción de neuropatías periféricas (sensorial y motriz) que debe resultar de ≤Grado 2. |
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E.4 | Principal exclusion criteria |
- Subjects who have not achieved disease-free status (e.g. no evidence of measurable disease or non-measurable disease per RECIST 1.1) after completion of CCRT administered with curative intent. - Subjects with FIGO stage IVB - Histologies other than described above (neuroendocrine cancers are excluded) - Subjects who have undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy NOTE: Women who have had a partial/subtotal hysterectomy are eligible to participate in the study. - Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (e.g. Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant. - Who are receiving, plan, or anticipate on receiving PI3K or TNF�� inhibitors. - Has a contraindication (sensitivity or allergy) to trimethoprim/sulfamethoxazole and ampicillin. |
• Las pacientes que no hayan alcanzado el estado libre de enfermedad (por ejemplo, no hay evidencia de enfermedad medible o enfermedad no medible según RECIST 1.1) después de terminar la quimiorradioterapia administrada con intención curativa. • Pacientes con etapa FIGO IVB • Histologías distintas a las descritas anteriormente (se excluyen los cánceres neuroendocrinos) • Pacientes que se hayan sometido a una histerectomía previa definida como la extracción de todo el útero o que se vayan a realizar una histerectomía como parte de su terapia inicial contra el cáncer de cuello uterino. NOTA: Las mujeres que se hayan realizado una histerectomía parcial/subtotal son elegibles para participar en el estudio. • Pacientes que se hayan implantado dispositivos médicos que presenten un riesgo alto de colonización y/o no se puedan quitar fácilmente (por ejemplo, articulaciones protéticas, válvulas del corazón artificiales, marcapasos, tornillos ortopédicos, placas de metal, injertos de huesos u otros implantes exógenos). NOTA: Se permiten los dispositivos y prótesis más comunes que incluyen stents arteriales y venosos, implantes dentales y de mama y dispositivos de acceso a las venas (por ejemplo, Port-a-Cath o Mediport). Se debe contactar con el Promotor antes de pedir el consentimiento a una paciente que tenga otro tipo de dispositivo y/o implante. Quienes están recibiendo, planificando recibir o creen que recibirán inhibidores de PI3K o TNF�� • Tiene una contraindicación (sensibilidad o alergia) a trimetoprim/sulfametoxazol y ampicilina. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is DFS measured from the time of randomization to recurrence or death. |
El objetivo primario de este estudio es la supervivencia sin enfermedad (DFS, por sus siglas en inglés) medida desde el momento de asignación aleatoria hasta la muerte o recidiva. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS evaluated using RECIST 1.1 methodology every 3 months, beginning 3 months after the first dose, for the first 2 years and then every 6 months for up to a total of 5 years; |
Las pacientes que no hayan alcanzado el estado libre de enfermedad medible según RECIST 1.1 metodología de evaluación cada 3 meses, comenzando 3 meses después de la primera dosis los 2 primeros años y luego cada 6 meses por un total de 5 años. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoint: OS (Overall survival) |
Objetivos secundarios de eficacia Supervivencia global (OS, por sus siglas en inglés). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS evaluated Approximately during 5 years |
Supervivencia global (OS) evaluado aproximádamente por 5 años |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Argentina |
Brazil |
Canada |
Chile |
Malaysia |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
Serbia |
Spain |
Taiwan |
Ukraine |
United States |
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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
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LVLS |
Última Visita del Último Paciente |
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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 | 5 |
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 | 5 |