E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platinum Resistant Ovarian Cancer |
Cáncer de Ovario resistente al platino |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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 efficacy of DNIB0600A compared with pegylated liposomal doxorubicin (PLD) in patients with PROC as assessed by PFS in patients with NaPi2b-high tumors as well as in the overall patient population. |
Evaluar la eficacia de DNIB0600A en comparación con DLP en pacientes con CORP, según lo determinado mediante la SSP evaluada por el investigador, en pacientes con tumores con NaPi2b elevado, así como en la población total de pacientes. |
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E.2.2 | Secondary objectives of the trial |
?To evaluate the efficacy of DNIB0600A compared with PLD in patients with PROC as assessed by overall survival (OS) in patients with NaPi2b-high tumors as well as in the overall patient population ?To evaluate the anti-tumor activity of DNIB0600A compared with PLD in patients with PROC as assessed by overall response rates and duration of response in patients with NaPi2b-high tumors as well as in the overall patient population ?To evaluate the safety and tolerability of DNIB0600A compared with PLD in patients with PROC |
- Evaluar la eficacia de DNIB0600A en comparación con DLP en pacientes con CORP, según lo determinado mediante la SG en pacientes con tumores con NaPi2b elevado, así como en la población total de pacientes. - Evaluar la actividad antitumoral de DNIB0600A en comparación con DLP en pacientes con CORP, según lo determinado mediante las tasas de respuesta global y la duración de la respuesta en pacientes con tumores con NaPi2b elevado, así como en la población total de pacientes. - Evaluar la seguridad y la tolerabilidad de DNIB0600A en comparación con DLP en pacientes con CORP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Signed informed consent form ? Age ? 18 years ? Life expectancy of at least 12 weeks ? Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 ? Histological documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding carcinosarcoma histology) ? Availability and willingness to provide an adequate archival sample of tumor (paraffin tissue block or at least 15 unstained slides); if an archival tissue specimen is not available and a new tissue specimen is collected for diagnostic purposes for patient care, then fresh tissue may be submitted ? Advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer that has progressed or relapsed during or within 6 months after the most recent treatment with a platinum-containing chemotherapy regimen and for whom pegylated liposomal doxorubicin (PLD) is appropriate ? Measurable disease with at least one lesion that can be accurately measured in at least one dimension (longest dimension recorded ? 2.0 cm using conventional techniques or ? 1.0 cm on spiral computed tomography [CT] scan) per RECIST v1.1 criteria ? No more than one prior cytotoxic chemotherapy regimen for the treatment of PROC and no more than two total regimens (defined as any therapy [approved or investigational] with intent to treat the ovarian cancer) ? Absolute neutrophil count ? 1500/?L, hemoglobin ? 9 g/dL, and platelet count ? 100,000/?L ? Total bilirubin ? 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 ×ULN ? Serum creatinine ? 2.0 mg/dL |
- Documento de consentimiento informado firmado. - Edad ? 18 años. - Esperanza de vida de 12 semanas, como mínimo. - Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1. - Confirmación histológica de un cáncer epitelial de ovario, cáncer peritoneal primario o cáncer de trompa de Falopio (excluida la histología de carcinosarcoma). - Disponibilidad y voluntad de proporcionar una muestra de archivo adecuada del tumor (bloque de tejido incluido en parafina o al menos 15 láminas sin teñir); cuando no se disponga de una muestra de tejido de archivo y se obtenga una nueva muestra de tejido con fines diagnósticos para la asistencia de la paciente, podrá enviarse tejido reciente. - Cáncer epitelial de ovario, peritoneal primario o de trompa de Falopio avanzado haya presentado progresión o recidiva en los 6 meses siguientes al tratamiento más reciente con un régimen de quimioterapia con platino y en el que DLP constituya un tratamiento adecuado. - Enfermedad mensurable con al menos una lesión que pueda medirse con exactitud en al menos una dimensión (dimensión más larga registrada ? 2,0 cm con técnicas convencionales o ? 1,0 cm en la tomografía computarizada [TC] helicoidal) según los criterios RECIST, versión 1.1. - No más de un régimen previo de quimioterapia citotóxica para tratar el CORP y no más de dos regímenes en total (definidos como cualquier tratamiento [aprobado o en investigación] con intención de tratar el cáncer de ovario). - Recuento absoluto de neutrófilos ? 1500/?l, hemoglobina ? 9 g/dl y recuento de plaquetas ? 100.000/?l. 11. Bilirrubina total ? 1,5 veces el límite superior de la normalidad (LSN); valores de aspartato aminotransferasa (AST) y alanina aminotransferasa (ALT) ? 2,5 veces el LSN. - Creatinina sérica ? 2,0 mg/dl. |
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E.4 | Principal exclusion criteria |
Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy, within 4 weeks prior to Day 1 ? Palliative radiation within 2 weeks prior to Day 1 ? Prior anthracycline therapy, including prior treatment with pegylated liposomal doxorubicin (PLD) (e.g., Doxil, Caelyx,? Prior treatment with NaPi2b or SCL34A2 targeted therapy ? Major surgical procedure within 4 weeks prior to Day 1 ? Current Grade > 1 toxicity (except alopecia and anorexia) from prior therapy or Grade > 1 neuropathy from any cause ? Left ventricular ejection fraction (LVEF) defined by MUGA/ECHO below the institutional lower limit of normal (LLN) ? Evidence of significant, uncontrolled, concomitant disease which could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease, history of bronchospasm, or any ongoing requirement for supplemental oxygen) |
- Tratamiento antitumoral, incluida quimioterapia y tratamiento biológico, experimental u hormonal, en las 4 semanas previas al día 1. - Radioterapia paliativa en las 2 semanas previas al día 1. - Tratamiento previo con antraciclinas, incluido el tratamiento previo con DLP (por ejemplo, Doxil, Caelyx) - Tratamiento previo con una terapia dirigada contra NaPi2b o SCL34A2. - Intervención de cirugía mayor en las 4 semanas previas al día 1. - Toxicidad presente de grado > 1 (excepto alopecia y anorexia) por el tratamiento previo o neuropatía de grado > 1 por cualquier causa. - Fracción de eyección del ventrículo izquierdo (FEVI) definida mediante ventriculografía isotópica en equilibrio (MUGA) o ecocardiograma por debajo del límite inferior de la normalidad (LIN). - Datos de enfermedades concomitantes, importantes y no controladas que puedan afectar al cumplimiento del protocolo o la interpretación de los resultados, entre ellas, enfermedades cardiovasculares importantes (como cardiopatía en clase III o IV de la New York Heart Association, insuficiencia cardíaca congestiva, infarto de miocardio en los 6 últimos meses, arritmias inestables o angina de pecho inestable) o enfermedades pulmonares importantes (como enfermedad pulmonar obstructiva, antecedentes de broncoespasmo o necesidad persistente de oxígeno suplementario). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-assessed progression-free survival (PFS) in patients with NaPi2b-high tumors as well as in all patients |
Supervivencia sin progresión (SSP) evaluada por el investigador en pacientes con tumores con NaPi2b elevado, así como en la población total de pacientes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening and every 8 weeks until discontinuation of the study treatment |
Evaluaciones de la respuesta cada 8 semanas hasta la discontinuación del tratamiento. |
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E.5.2 | Secondary end point(s) |
-Overall survival (OS) in patients with NaPi2b-high tumors as well as in all patients -Investigator-assessed overall response rate (ORR) in patients with NaPi2b-high tumors as well as in all patients -Safety and tolerability |
- Supervivencia global en pacientes con tumores con NaPi2b elevado, así como en la población total de pacientes. - Supervivencia sin progresión, evaluada por el investigador en pacientes con tumores con NaPi2b elevado, así como en la población total de pacientes. - Seguridad y tolerabilidad. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Throughout the study treatment and every 3 months until death, loss to follow-up, or study closure -Screening and every 8 weeks until discontinuation of the study treatment -Throughout the study treatment until 30 days after the last dose of either DNIB0600A or PLD |
- Durante el tratamiento del estudio y cada 3 meses hasta que se produzca la muerte, pérdida para el seguimiento o suspensión del estudio. - Evaluaciones de la respuesta cada 8 semanas hasta la discontinuación del tratamiento. - Durante el tratamiento del estudio y hasta 30 días después de la última dosis de DNIB0600A o PLD. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
multicentre and open-label study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Canada |
France |
Poland |
Spain |
United Kingdom |
United States |
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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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The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later. LPLV is expected to occur 1 year after the last patient is enrolled. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |