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PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma

19 de diciembre de 2018 actualizado por: Pfizer

A PHASE II TRIAL OF PF-04856884 (CVX-060), A SELECTIVE ANGIOPOIETIN-2 (ANG-2) INHIBITOR IN COMBINATION WITH AG-013736 (AXITINIB) IN PATIENTS WITH PREVIOUSLY TREATED METASTATIC RENAL CELL CARCINOMA

To evaluate the combination of PF-04856884 (CVX-060) in combination with Axitinib (AG-013736) in patients that have received one prior systemic regimen for metastatic renal cell carcinoma (mRCC) vs. axitinib alone.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

The study was prematurely discontinued on 06Nov2012 due to tolerability findings in patients treated in Part I of the study that have prompted the Sponsor to re-evaluate the strategic development of the program. An unexpected frequency of arterial thrombotic events (ATEs) and venous thrombotic events (VTEs) were reported in patients treated in Part I.

Tipo de estudio

Intervencionista

Inscripción (Actual)

18

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Chequia
      • Brno, Chequia, 65653
        • Masarykuv Onkologicky Ustav
  • Estados Unidos
    • Arizona
      • Scottsdale, Arizona, Estados Unidos, 85258
        • Pinnacle Oncology Hematology
      • Tucson, Arizona, Estados Unidos, 85704
        • Arizona Oncology Associates, PC - HOPE
      • Tucson, Arizona, Estados Unidos, 85710
        • Arizona Oncology Associates, PC-Hope
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80012
        • Rocky Mountain Cancer Centers
      • Boulder, Colorado, Estados Unidos, 80303
        • Rocky Mountain Cancer Centers
      • Centennial, Colorado, Estados Unidos, 80112
        • Rocky Mountain Cancer Centers
      • Colorado Springs, Colorado, Estados Unidos, 80907
        • Rocky Mountain Cancer Centers
      • Colorado Springs, Colorado, Estados Unidos, 80909
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, Estados Unidos, 80218
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, Estados Unidos, 80220
        • Rocky Mountain Cancer Centers
      • Lakewood, Colorado, Estados Unidos, 80228
        • Rocky Mountain Cancer Centers
      • Littleton, Colorado, Estados Unidos, 80120-4413
        • Rocky Mountain Cancer Centers
      • Lone Tree, Colorado, Estados Unidos, 80124
        • Rocky Mountain Cancer Centers
      • Longmont, Colorado, Estados Unidos, 80501
        • Rocky Mountain Cancer Centers
      • Parker, Colorado, Estados Unidos, 80138
        • Rocky Mountain Cancer Centers
      • Pueblo, Colorado, Estados Unidos, 81008
        • Rocky Mountain Cancer Centers
      • Thornton, Colorado, Estados Unidos, 80260
        • Rocky Mountain Cancer Centers
    • Nebraska
      • Omaha, Nebraska, Estados Unidos, 68114
        • Nebraska Methodist Hospital
    • Nevada
      • Henderson, Nevada, Estados Unidos, 89074
        • Comprehensive Cancer Centers of Nevada
      • Henderson, Nevada, Estados Unidos, 89052
        • Comprehensive Cancer Centers of Nevada
      • Henderson, Nevada, Estados Unidos, 89014
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, Estados Unidos, 89148
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, Estados Unidos, 89128
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, Estados Unidos, 89169
        • Comprehensive Cancer Centers of Nevada
    • North Carolina
      • Durham, North Carolina, Estados Unidos, 27704
        • Regional Cancer Care-Durham
    • Texas
      • Tyler, Texas, Estados Unidos, 75702
        • Texas Oncology-Tyler
    • Washington
      • Seattle, Washington, Estados Unidos, 98109
        • Seattle Cancer Care Alliance
      • Seattle, Washington, Estados Unidos, 98195
        • University of Washington Medical Center

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Adult male or female patients with histologically or cytologically confirmed renal cell cancer (RCC) with a component of clear cell subtype and evidence of metastasis
  • Evidence of unidimensionally measurable disease
  • Prior therapy: Part I: Having received 1 to 3 prior systemic regimens for treatment of mRCC
  • Part II: Evidence of disease progression following 1 prior regimen administered as 1st line therapy for mRCC. The prior regimen must have contained one of the following: VEGFR2 tyrosine kinase inhibitor (TKI) or other anti VEGF [Vascular Endothelial Growth Factor] compounds, such as bevacizumab
  • adequate bone marrow, liver and renal function

Exclusion Criteria:

Part I:

  • Intolerant to prior AG 013736 therapy or prior treatment with compounds which contain the core platform antibody as PF 04856884

Part II:

  • Prior AG 013736 therapy, more than one systemic first-line regimen for the treatment of mRCC and prior treatment with compounds which contain the core platform antibody as PF 04856884
  • major surgery <4 weeks or radiation therapy <2 weeks prior to start of therapy
  • clinically significant gastrointestinal abnormalities
  • current use or anticipated need for drugs that are known potent CYP3A4 inhibitors and drugs that are known CYP3A4 or CYP1A2 inducers
  • history of bleeding diathesis or coagulopathy
  • Grade 3 or greater hemorrhage from any cause <4 weeks prior to screening;
  • hemoptysis >½ teaspoon of blood per day within 2 weeks prior to screening.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: ARM A
PF-04856884 in combination with AG-013736
Biológico: PF-04856884
15 mg/kg/week intravenously [IV] until toxicity or disease progression
Droga: Axitinib (AG-013736)
5 mg PO BID
Comparador activo: ARM B
AG-013736 alone
Droga: Axitinib (AG-013736)
5 mg PO BID

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall).
Periodo de tiempo: 4 months

Incidence and severity of all treatment-emergent AEs (TEAEs) of both all-causality and treatment-related by preferred term (PT) categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades reported in ≥2 participants overall (CTCAE Grades 3, 4 and 5, combined) for any PT are presented. Participants who are included under all-causality TEAE PT are coded as NA if they appear for the same PT under treatment-related TEAE below.

Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
4 months
Number of Participants With Serious Adverse Events (SAEs) in Part I
Periodo de tiempo: 4 months
Incidence and severity of all-causality serious adverse events (SAEs) are presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week). Participants with treatment-related TEAE are coded as NA if they appear for the same preferred term under all-causality TEAE.
4 months
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) in Part II
Periodo de tiempo: 3 years
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. Progression free survival was to be calculated as (first event date - the date of randomization +1).
3 years

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants With Non-serious AEs and SAEs
Periodo de tiempo: 3 years
Incidence and severity of all-causality AEs and SAEs to be presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
3 years
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone.
Periodo de tiempo: 4 months
ORR is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), relative to all randomized participants as defined in the FA Set. Confirmed responses are those that persist on repeat imaging study ≥ 4 weeks after initial documentation of response. Participants who do not have on-study radiographic tumor evaluation or who die, progress, or drop out for any reason prior to reaching a CR or PR will be counted as non-responders (NR) in the assessment of ORR.
4 months
Duration of Response (DR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone
Periodo de tiempo: 3 years
DR is defined as the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of tumor progression or to death due to cancer. Duration of tumor response was to be calculated as (the end date for DR - first CR or PR that is subsequently confirmed +1).
3 years
Tmax (Time When Maximum Serum PF-04856884 Concentration Was Reached)
Periodo de tiempo: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Pharmacokinetic parameter, Tmax (Time when maximum serum PF-04856884 concentration was reached) was done using non-compartmental methods.
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Cmax (Observed Peak Serum PF-04856884 Concentration)
Periodo de tiempo: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Pharmacokinetic parameter Cmax (observed peak PF-04856884 serum concentration) was estimated using noncompartmental methods.
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Cmin (Trough PF-04856884 Serum Concentration)
Periodo de tiempo: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Pharmacokinetic parameter Cmin (trough PF-04856884 serum concentration) was estimated using noncompartmental methods.
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Number of Anti-drug Antibodies (ADA) Samples Confirmed Positive
Periodo de tiempo: 0 and 360 hours post dose and end of study
Detection of neutralizing anti-PF-04856884 antibodies was based on the ability of anti-PF-04856884 neutralizing antibodies to bind to Tag-PF-04856884.
0 and 360 hours post dose and end of study
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) as Measured by an Independent Radiological Assessment
Periodo de tiempo: 3 years
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. PFS was to be calculated as (first event date - the date of randomization +1).
3 years
Overall Survival (OS) at 2 Years
Periodo de tiempo: 5 years
OS is defined as the time from the first dose date to date of death. For participants not expiring, their survival times will be censored at the last date they are known to be alive, or 2 year whichever is earlier. The 2-year OS rate will be estimated from a time-to event analysis of OS.
5 years

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Pfizer

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

21 de noviembre de 2011

Finalización primaria (Actual)

27 de marzo de 2014

Finalización del estudio (Actual)

27 de marzo de 2014

Fechas de registro del estudio

Enviado por primera vez

26 de agosto de 2011

Primero enviado que cumplió con los criterios de control de calidad

23 de septiembre de 2011

Publicado por primera vez (Estimar)

27 de septiembre de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de enero de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

19 de diciembre de 2018

Última verificación

1 de diciembre de 2018

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • B1131004
  • 2011-002190-33 (Número EudraCT)

Plan de datos de participantes individuales (IPD)

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Descripción del plan IPD

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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