E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma |
Adenocarcinoma ductal pancreático en estadio IV con elevación de hialuronano no tratado previamente |
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E.1.1.1 | Medical condition in easily understood language |
Previously Untreated Pancreatic Cancer with High Levels of Hyaluronan |
Cáncer pancreático con altos niveles de hialuronano no tratado previamente |
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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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007050 |
E.1.2 | Term | Cancer |
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 determine the progression-free survival (PFS) benefit of PEGPH20 combined with nab-paclitaxel (NAB) plus gemcitabine (GEM) (PAG treatment), compared with placebo plus NAB/GEM (AG treatment), in subjects with hyaluronan (HA)-high Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA)
-To determine the overall survival (OS) benefit of PAG treatment, compared with AG treatment, in subjects with HA-high Stage IV previously untreated PDA |
-Determinar el beneficio en cuanto a supervivencia sin progresión (SSP) de la PEGPH20 combinada con NAB y GEM (tratamiento PAG), en comparación con placebo más NAB/GEM (tratamiento AG), en sujetos con ADP en estadio IV con elevación de hialuronano no tratados previamente.
-Determinar el beneficio en cuanto a SG del tratamiento PAG, comparado con el tratamiento AG, en sujetos con ADP en estadio IV con elevación de hialuronano no tratados previamente. |
|
E.2.2 | Secondary objectives of the trial |
-To determine the objective response rate (ORR) and duration of response (DOR) of PAG treatment, compared with AG treatment, in subjects with HA-high Stage IV previously untreated PDA
-To assess the safety and tolerability of PAG treatment in subjects with HA-high Stage IV previously untreated PDA |
-Determinar la TRO y la DDR del tratamiento PAG, comparado con el tratamiento AG, en sujetos con ADP en estadio IV con elevación de hialuronano no tratados previamente.
-Evaluar la seguridad y la tolerabilidad del tratamiento PAG en sujetos con ADP en estadio IV con elevación de hialuronano no tratados previamente. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form (ICF). 2. Stage IV pancreatic ductal adenocarcinoma (PDA) with histological confirmation of PDA via archived or fresh core biopsy of either the primary tumor or 1 metastatic in minimum of 5-10 unstained core biopsy slides that meet specific tissue sample requirements are required. 3. Subjects must be determined to be HA-high based on tumor biopsy that meets the requirements noted in inclusion criteria #2. 4. If a subject has had adjuvant therapy (chemotherapy for non-metastatic pancreatic cancer in combination with or without radiation therapy), tumor recurrence or disease progression must have occurred no sooner than 6 months after completing the last dose of adjuvant therapy, provided all toxicities have returned to baseline or < = Grade 1. |
1. Firma del documento de consentimiento informado aprobado por el comité ético de investigación clínica (CEIC)/Institutional Review Board (IRB). 2. Hialuronano Adenocarcinoma ductal pancreático (ADP) en estadio IV con confirmación histológica de ADP mediante biopsia con aguja gruesa, de archivo o reciente, del tumor primario o 1 localización metastásica en un mínimo de 5-10 laminillas de FFIP consecutivas no teñidas de 1 bloque de archivo que cumplan los requisitos específicos para muestras tisulares. 3. Los sujetos deberán presentar elevación de hialuronano determinada en una biopsia tumoral que cumpla los requisitos indicados en el criterio de inclusión previo. 4. Si un sujeto ha recibido tratamiento adyuvante (quimioterapia para el cáncer pancreático no metastásico con o sin radioterapia en combinación), la recidiva tumoral o la progresión de la enfermedad debe haberse producido no antes de 6 meses después de terminar la última dosis de tratamiento adyuvante, siempre que todas las toxicidades hayan vuelto a la situación basal o a grado < 1. |
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E.4 | Principal exclusion criteria |
1. Clinical evidence of DVT, PE or other known TE event present during the screening period. 2. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. a. Palliative radiotherapy for pain control of metastatic bone lesions is allowed. 3. Known central nervous system involvement or brain metastases. 4. New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months. 5. History of cerebrovascular accident or transient ischemic attack. 6. Pre-existing carotid artery disease. |
1. Manifestaciones clínicas de trombosis venosa profunda (TVP), embolia pulmonar (EP) u otro acontecimiento TE conocido durante el periodo de selección. 2. Tratamiento previo de metástasis con radioterapia, cirugía, quimioterapia o terapia en investigación. a.Se permite la radioterapia paliativa para el control del dolor de las lesiones óseas metastásicas. 3. Afectación conocida del sistema nervioso central o metástasis cerebrales. 4. Cardiopatía de clase III o IV de la New York Heart Association (NYHA) o infarto de miocardio en los últimos 12 meses. 5. Antecedentes de accidente cerebrovascular o accidente isquémico transitorio. 6. Arteriopatía carotídea preexistente. |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Progression-free survival -Overall survival |
-Supervivencia sin progresión -Supervivencia global |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Final PFS will be conducted at the interim when a pre-specified number of PFS events have occurred. Final OS analysis will be conducted at the end of the study. During long-term follow-up information on the subject?s survival and subsequent anticancer therapy will be obtained by the site every 3 months until the subject dies, is lost to follow-up, or withdraws consent. Subjects will be censored for OS at the time of the last ?known alive? contact. The OS analysis will be conducted at the end of the study. |
El análisis intermedio de la supervivencia sin progresión (SSP) final se llevará a cabo cuando un número predeterminado de eventos de SSP haya ocurrido. El análisis de supervivencia global se llevará a cabo al final del estudio.
Después de la Visita de Fin del Tratamiento, los sujetos entrarán en un seguimiento a largo plazo en el que el centro recabará información sobre la supervivencia y el tratamiento antineoplásico posterior del sujeto cada 3 meses hasta que el sujeto fallezca, se pierda para el seguimiento o revoque su consentimiento. Los sujetos serán censurados estadísticamente para supervivencia global en el momento del último contacto en que se supo que el sujeto seguía vivo . El análisis de supervivencia global se llevará a cabo al final del estudio. |
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E.5.2 | Secondary end point(s) |
-Objective response rate -Duration of response -Incidence of AEs, changes in clinical safety laboratory values, and changes in cardiovascular parameters (electrocardiogram [ECG] and vital signs) |
-Tasa de respuesta objetiva -Duración de la respuesta -Incidencia de AA, cambios de los valores de los análisis clínicos de laboratorio con fines de seguridad y cambios de los parámetros cardiovasculares (ECG y constantes vitales) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Refer to protocol for information. |
Para más información consulten el protocolo. |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 103 |
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 |
Brazil |
Canada |
China |
Croatia |
Czech Republic |
Denmark |
Estonia |
France |
Germany |
Hungary |
Israel |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Netherlands |
Poland |
Spain |
Taiwan |
United Kingdom |
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
|
The end of the study is defined by the final OS analysis, i.e. when the specified number of events (deaths) is reached. |
El final del estudio se define por el análisis final de la SG, esto es, cuando se alcance el número especificado de acontecimientos (muertes) |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |