E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced ovarian granulosa unresectable or metastatic tumor |
Cáncer de la granulosa ovárica avanzado no resecable o metastásico |
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E.1.1.1 | Medical condition in easily understood language |
Ovarian granulosa tumor |
Cáncer de la granulosa ovárica |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of enzalutamide in advanced ovarian granulosa unresectable or metastatic tumor by the overall response rate (ORR), defined as the percentage of patients achieving partial or complete response according to RECIST 1.1 criteria, by means of radiological evaluation. |
Evaluar la eficacia de enzalutamida en tumores de la granulosa ovárica avanzado no resecable o metastásico mediante la tasa de respuesta global (TRG), definida como el porcentaje de pacientes que alcanzan una respuesta parcial o completa según los criterios RECIST 1.1, mediante evaluación radiológica. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the clinical benefit rate, defined as the stabilization of disease for at least 6 months, plus the sum of partial and complete responses according to RECIST 1.1 criteria, by means of radiological evaluation. - To evaluate progression-free survival (PFS), defined as time from the administration of the first dose of treatment to the progression of the disease according to RECIST 1.1 criteria or death of the patient for any cause. - To evaluate overall survival (OS), defined as the time since the administration of the first dose of treatment until the death of the patient for any cause. - To determine the toxicity profile of enzalutamide in the population of the study. |
- Evaluar la tasa de beneficio clínico, definida como estabilización de la enfermedad durante al menos 6 meses, más la suma de respuestas parciales y completas según los criterios RECIST 1.1, mediante evaluación radiológica. - Evaluar la supervivencia libre de progresión (SLP), definida como el tiempo desde la administración de la primera dosis del tratamiento hasta la progresión de la enfermedad según los criterios RECIST 1.1 o la muerte de la paciente por cualquier causa. - Evaluar la supervivencia global (SG), definida como el tiempo desde la administración de la primera dosis del tratamiento hasta la muerte de la paciente por cualquier causa. - Determinar el perfil de toxicidad de enzalutamida en la población del estudio.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have given written informed consent 2. Women aged 18 years or over 3. ECOG ≤ 1 4. Diagnosis of histologically confirmed ovarian granulosa carcinoma. 5. Availability of sufficient biopsy material for confirmation of the diagnosis by a centralized pathologist and determination of the mutation FOXL2402C→ G(C134W). If this material is not available, principal investigator of the study will confirm eligibility of the patient. 6. Metastatic or unresectable disease 7. Radiologically measurable disease. In case you there is not measurable disease, principal investigator of the study will confirm eligibility of the patient. 8. Life expectancy ≥ 12 weeks. 9. Patients with adequate hepatic function, defined by: - AST and ALT serum values ≤ 3 x ULN (except in the presence of metastasis in which case values ≤ 5 x ULN will be allowed) - Total bilirubin values ≤1,5 x ULN 10. Patients with adequate bone marrow function, defined by: - Absolute neutrophil count ≥1.5 x 109 / L - Platetets ≥100 x 109/L, - Hemoglobine ≥9 g/dL. 11. Patients with adequate renal function: serum creatinine ≤1,5 x LSN 12. Absence of any disability to follow the study protocol. 13. Women childbearing potential who are sexually active, not undergoing hysterectomy or double adnexectomy, should follow the following contraceptive indications: - Negative Pregnancy Test in serum or urine in the 72 hours before the start of treatment. - Use of a medically accepted method of contraception during: 2 months prior to the start of study treatment, during the study and up to 3 months after the last dose of treatment. |
1. Pacientes que hayan otorgado su consentimiento informado por escrito 2. Mujeres con edad igual o superior a 18 años 3. ECOG ≤1 4. Diagnóstico de carcinoma de la granulosa ovárica confirmado histológicamente 5. Disponibilidad de material de biopsia suficiente para la confirmación del diagnóstico por un patólogo centralizado y determinación de la mutación FOXL2 402C→G (C134W). En caso de no disponerse de este material, se consultará con el investigador coordinador la elegibilidad del caso. 6. Enfermedad metastásica o no resecable 7. Enfermedad medible radiológicamente. En caso de no presentar enfermedad medible, se consultará con el investigador coordinador la elegibilidad del caso. 8. Esperanza de vida ≥ 12 semanas. 9. Pacientes con adecuada función hepática, definida por: - Valores séricos de AST y ALT ≤ 3 x LSN (salvo en presencia de metástasis en cuyo caso se permitirán valores ≤ 5 x LSN) - Valores de bilirrubina total ≤1,5 x LSN 10. Pacientes con adecuada función de la médula ósea, definida por: - Recuento absoluto de neutrófilos ≥1,5 x 109/L, - Plaquetas ≥100 x 109/L, - Hemoglobina ≥9 g/dL. 11. Pacientes con función renal adecuada: creatinina sérica ≤1,5 x LSN 12. Ausencia de cualquier impedimento para el cumplimiento del protocolo del estudio 13. Las mujeres en edad fértil sexualmente activas, no sometidas a histerectomía o doble anexectomía, deben seguir las siguientes indicaciones sobre contracepción: - Prueba del embarazo en suero u orina negativa en las 72 horas anteriores al inicio del tratamiento. - Utilización de un método anticonceptivo médicamente aceptado durante: los 2 meses anteriores al inicio del tratamiento del estudio, durante el estudio y hasta 3 meses después de la última dosis del tratamiento. |
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E.4 | Principal exclusion criteria |
1. Patients with another primary tumor 2 years before beginning the drug under study, with the exception of adequetely treated or totally surgically removed cervical carcinoma in-situ or basaliome or superficial bladder carcinoma. 2. Patients who have received radical radiotherapy ≤ 4 weeks prior to the start of study treatment or who have not recovered from toxicities of radiotherapy. Palliative radiation therapy for painful bone lesions bone is allowed up to 14 days prior to the beginning of the study treatment 3. History of seizures or any conditions that may predispose to suffer them. 4. Current or previously treated brain metastases or disease leptomeningea. 5. Patients with cardiac insufficiency or heart disease clinically significant ncluding any of the following: - History or presence of uncontrolled severe ventricular arrhythmias. - Clinically significant resting bradycardia. - Any of the following diseases within 6 months prior to the start of the study drug Myocardial infarction (MI), severe or unstable angina, coronary revascularization, congestive cardiac insufficiency (CCI), cerebrovascular accident (CVA), transient ischemic accident (TIA) 6. Patients with altered gastrointestinal function or with gstric disease that significantly alters the absorption of enzalutamide, such as for example: severe ulcer diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, extensive resection (> 1m) of the small bowel or inability to swallow oral medication. The previous partial or total gastrectomy is not an exclusion criterion. 7. Diagnosis of human immunodeficiency virus (HIV) infection. 8. Pregnant or lactating women. 9. Women of childbearing potential not using an effective contraceptive method. 10. Patients who do not want or can follow the study protocol. |
1. Pacientes con otro tumor primario 2 años antes de comenzar con el fármaco en estudio, con la excepción de carcinoma de cuello de útero in-situ adecuadamente tratado o extirpado completamente o basalioma o carcinoma vesical superficial. 2. Pacientes que hayan recibido radioterapia radical ≤ 4 semanas antes de comenzar el tratamiento en estudio o que no se hayan recuperado de las toxicidades de la radioterapia. La radioterapia paliativa para las lesiones dolorosas de hueso está permitida hasta 14 días previos al comienzo del tratamiento en estudio. 3. Antecedentes de convulsiones o cualquier condición que pueda predisponer a sufrirlas. 4. Metástasis cerebrales actuales o previamente tratadas o enfermedad leptomeningea. 5. Pacientes con insuficiencia cardiaca o enfermedad cardiaca clínicamente significativas, incluyendo cualquiera de las siguientes: - Historia o presencia de arritmias ventriculares severas no controladas. - Bradicardia en reposo clínicamente significativa. - Cualquiera de las siguientes enfermedades dentro de los 6 meses previos al comienzo del fármaco en estudio: Infarto de miocardio (IM), angina severa o inestable, revascularización coronaria, insuficiencia cardiaca congestiva (ICC), accidente cerebrovascular (ACV), accidente isquémico transitorio (TIA). 6.Pacientes con alteración de la función gastrointestinal o con enfermedad gástrica que altere significativamente la absorción de enzalutamida, como por ejemplo: enfermedades ulcerosas graves, náuseas descontroladas, vómitos, diarrea, síndrome de malabsorción, resección extensa (>1m) del intestino delgado o incapacidad para tragar medicación oral. La gastrectomía previa parcial o total no es un criterio de exclusión. 7.Diagnóstico de infección por el virus de la inmunodeficiencia humana (VIH). 8. Mujeres embarazadas o en lactancia. 9. Mujeres en edad fértil que no empleen un método anticonceptivo efectivo. 10. Pacientes que no quieran o no puedan cumplir con el protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Rate Response (ORR) |
Tasa de respuesta global (TRG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Achivement of partial or complete response according to RECIST 1.1 criteria, by means of radiological evaluation. |
Momento en que se alcanza respuesta parcial o completa según los criterios RECIST 1.1, mediante evaluación radiológica. |
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E.5.2 | Secondary end point(s) |
- Clinical Benefit Rate - Progression Free Survival (PFS) - Overall Survival (OS) - Toxicity to Enzalutamide
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- Tasa de beneficio clínico - Supervivencia libre de progresión (SLP) - Supervivencia global (SG) - Toxicidad de enzalutamida
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Clinical Benefit Rate, achivement of stabilization of the disease during at least 6 months and achievement of both partial and complete responses - Progression Free Survival (PFS), achivement of progression diseases since first administration of the study drug - Overall Survival (OS), achivement of the death of the patient for any cause since first administration of the study drug - Toxicity to Enzalutamide, since first administration of the study drug until the end of the study treatment. |
- Tasa de beneficio clínico, alcanzar estabilización de la enfermedad durante al menos 6 meses, más la suma de respuestas parciales y completas - Supervivencia libre de progresión (SLP), alcanzar progresion de la enfermedad desde la administración de la primera dosis del tratamiento del estudio. - Supervivencia global (SG), alcanzar el fallecimiento por cualquier causa desde la administración de la primera dosis del tratamiento del estudio. - Toxicidad de enzalutamida registrada desde la primer administración del tratamiento del estudio hasta la finalización del mismo.
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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) | 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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |