E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Desmoplastic small round cell tumour (DSRCT) |
Tumor desmoplásico de células pequeñas y redondas (TDCPR) |
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E.1.1.1 | Medical condition in easily understood language |
Desmoplastic small round cell tumour |
Tumor desmoplásico de células pequeñas y redondas |
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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 | 10064581 |
E.1.2 | Term | Desmoplastic small round cell tumour |
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 ramucirumab in combination with cyclophosphamide and vinorelbine compared with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT (DSRCT= desmoplastic small round cell tumor). |
Comparar la eficacia de ramucirumab en combinación con ciclofosfamida y vinorelbina con la de ciclofosfamida y vinorelbina en el tratamiento de pacientes menores de edad y adultos jóvenes con TDCPR (tumor desmoplásico de células pequeñas y redondas). |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of ramucirumab in combination with cyclophosphamide and vinorelbine compared with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT - To characterize the PK of ramucirumab when co-administered with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT - To assess the immunogenicity of ramucirumab when co-administered with cyclophosphamide and vinorelbine in pediatric and young adult patients with DSRCT |
-Comparar la seguridad y la tolerabilidad de ramucirumab en combinación con ciclofosfamida y vinorelbina con la de ciclofosfamida y vinorelbina en el tratamiento de pacientes menores de edad y adultos jóvenes con TDCPR. - Caracterizar la FC de ramucirumab cuando se administra de forma concomitante con ciclofosfamida y vinorelbina a pacientes menores de edad y adultos jóvenes con TDCPR. - Caracterizar la inmunogenia de ramucirumab cuando se administra de forma concomitante con ciclofosfamida y vinorelbina a pacientes menores de edad y adultos jóvenes con TDCPR. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The washout-period after previous antibody therapy is defined as 4 half-lives after the last dose of the antibody - Pediatric and young adult patients will be enrolled, where the specific age requirement for each indication will be specified in the protocol addenda. - Patients must be >11 kg at the time of study enrollment. - Patients with relapsed, recurrent, or refractory DSRCT. - Patients must be 36 months to ≤29 years of age at the time of study enrollment. - Patients must: •have measurable disease by RECIST 1.1 •have received at least one prior line of systemic treatment (including neoadjuvant and adjuvant chemotherapy). This prior treatment must include approved therapies for which they are eligible, unless the patient is not a suitable candidate for the approved therapy. •not be eligible for surgical resection at time of enrollment. - Patients who have a Lansky (<16 years of age; Lansky et al. 1987) or Karnofsky (≥16 years of age; Karnofsky et al. 1948) performance score of at least 50. - Patient with adequate hematologic, coagulation, liver, cardiac, renal and bladder function, and adequate blood pressure (BP) control as per protocol. |
-El período de reposo farmacológico tras el tratamiento previo con anticuerpos se define como 4 semividas desde la última dosis del anticuerpo. -Se reclutarán menores y adultos jóvenes. La edad específica para cada indicación se establecerá en la adenda al protocolo. -Los pacientes deben pesar más de 11 kg en el momento del reclutamiento en el estudio. - Pacientes con TDCPR recidivante, recurrente o resistente al tratamiento. - Pacientes de entre 36 meses y ≤29 años de edad en el momento del reclutamiento en el estudio. - Los pacientes deben: • presentar enfermedad mensurable de acuerdo con los criterios RECIST 1.1. • haber recibido al menos una línea previa de tratamiento sistémico (se contabiliza también la quimioterapia neoadyuvante y adyuvante). El tratamiento previo debe haber consistido en terapias aprobadas para las que el paciente sea tributario, a menos que este no sea un candidato idóneo para la terapia aprobada. • no ser tributarios de una intervención de resección quirúrgica en el momento del reclutamiento. - Pacientes con una puntuación del estado funcional de al menos 50 en la escala de Lansky (<16 años; Lansky et al. 1987) o en la de Karnofsky (≥16 años; Karnofsky et al. 1948).- El paciente debe tener una función hematológica, hepática, cardíaca, renal y vesical suficientes, así como una coagulación y un control de la tensión arterial (TA) aceptables, de conformidad con el protocolo. |
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E.4 | Principal exclusion criteria |
- Patients who have had allogeneic bone marrow or solid organ transplant are excluded. - Patients who have active infections requiring therapy. - Patients who have a history of fistula, gastrointestinal (GI) ulcer or perforation, or intra-abdominal abscess within 3 months of study enrolment are not eligible. - Patients with a bowel obstruction, extensive intestinal resection or history or presence of inflammatory enteropathy or other GI pathology as per protocol. - Patients with a history of hepatorenal syndrome. - Patients with evidence of active bleeding or a history of significant (≥Grade 3) bleeding event, deep vein thrombosis requiring medical intervention (including pulmonary embolism), hemoptysis or other signs of pulmonary haemorrhage, or esophageal varices within 3 months of enrollment are not eligible. - Patients with a bleeding diathesis or vasculitis are not eligible. - Patients with a history of central nervous system (CNS) arterial/venous thromboembolic events (VTEs) including transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months of study enrollment are not eligible. - Patients with myocardial infarction or unstable angina within the prior 6 months. - Patients with significant vascular disease or peripheral vascular disease. - Patients with a history of hypertensive crisis or hypertensive encephalopathy within 6 months of study enrollment are not eligible. - Patients who have non-healing wound, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrolment are not eligible. - Patients previously treated and progressed on combination cyclophosphamide and vinorelbine regimen. (Patients who received combination as maintenance therapy, without progression, would be eligible.) - Patients with a known hypersensitivity to ramucirumab, cyclophosphamide, vinorelbine or any of the excipients of the medicinal products. - Patients who have previously received any exposure to ramucirumab are not eligible. - Patients with CNS involvement are ineligible. |
-Se excluirá a los pacientes que hayan recibido un alotrasplante de médula ósea o un trasplante de víscera maciza. - Pacientes que presenten infecciones activas que requieran tratamiento. - No se considerarán idóneos los pacientes con antecedentes de fístulas, úlceras o perforaciones gastrointestinales (GI) o abscesos intraabdominales en el transcurso de los 3 meses anteriores al reclutamiento en el estudio. - Pacientes con obstrucción intestinal, amplia resección intestinal o antecedentes o presencia de enteropatía inflamatoria u otras patologías gastrointestinales, de conformidad con el protocolo. - Pacientes con antecedentes de síndrome hepatorrenal. - No se considerarán idóneos los pacientes con signos de hemorragia activa o antecedentes de episodios hemorrágicos importantes (grado ≥3), trombosis venosa profunda que requiera una intervención médica (incluidos los casos de embolia pulmonar), hemoptisis u otros signos de hemorragia pulmonar o varices esofágicas en el transcurso de los 3 meses anteriores al reclutamiento. - No se considerarán idóneos los pacientes con diátesis hemorrágica o vasculitis. - No se considerarán idóneos los pacientes con antecedentes de episodios tromboembólicos venosos/arteriales (ETV/ETA) en el sistema nervioso central, incluidos los casos de accidente isquémico transitorio (AIT) o de accidente cerebrovascular (ACV) en el transcurso de los 6 meses anteriores al reclutamiento en el estudio. - Pacientes que hayan sufrido un infarto de miocardio o angina de pecho inestable en el transcurso de los 6 meses anteriores. - Pacientes con vasculopatía o vasculopatía periférica importante. - No se considerarán idóneos los pacientes con antecedentes de crisis hipertensiva o encefalopatía hipertensiva en el transcurso de los 6 meses anteriores al reclutamiento en el estudio. - No se considerarán idóneos los pacientes que en el momento del reclutamiento presenten heridas tórpidas, fracturas sin consolidar o consolidadas parcialmente, o fracturas óseas abiertas. - Pacientes que anteriormente hayan recibido tratamiento politerápico con ciclofosfamida y vinorelbina y hayan sufrido progresión de la enfermedad durante este tratamiento (se considerarán idóneos para participar los pacientes que hayan recibido esta politerapia como tratamiento de mantenimiento y no hayan presentado progresión de la enfermedad). - Pacientes con hipersensibilidad a ramucirumab, ciclofosfamida, vinorelbina o cualquiera de los excipientes de los medicamentos. - No se considerarán idóneos los pacientes que anteriormente hayan recibido ramucirumab. - Los pacientes que presenten afectación en el SNC no se considerarán idóneos. |
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E.5 End points |
E.5.1 | Primary end point(s) |
progression-free survival (PFS) |
Supervivencia sin progresión (SSP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis will be triggered when PFS events have occurred for approximately 80% of the enrolled patients |
El análisis principal se realizará cuando se hayan observado eventos de SSP aproximadamente en el 80 % de los pacientes reclutados. |
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E.5.2 | Secondary end point(s) |
Serious adverse event, Adverse event, Safety laboratory assessments, Vital signs, Overall response rate, Duration of response, Complete response, Incidence of immunogenicity, Cmax (maximum concentration) and Cmin (minimum concentration) |
Acontecimientos adversos graves, acontecimientos adversos, parámetros analíticos de seguridad, constantes vitales, tasa global de respuesta, duración de la respuesta, respuesta completa, incidencia de casos de inmunogenia, Cmáx (concentración máxima) y Cmín (concentración mínima). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout study |
A lo largo del estudio. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 |
Therapeutic exploratory |
Exploratorio terapeutico |
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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 | 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 | 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) | 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 | 21 |
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 |
Australia |
Belgium |
France |
Germany |
Italy |
Japan |
Netherlands |
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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LVLS - Last visit or last scheduled procedure for the last patient. |
UVUP: última visita o último procedimiento programado 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 | 2 |
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 | 2 |
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 |