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Trebananib in Treating Younger Patients With Relapsed or Refractory Solid Tumors, Including Central Nervous System Tumors

30 de septiembre de 2016 actualizado por: National Cancer Institute (NCI)

A Phase 1 Study of AMG 386, an Angiopoietin Neutralizing Peptibody, in Children With Relapsed or Refractory Solid Tumors, Including CNS Tumors

This phase I trial studies the side effects and best dose of trebananib in treating patients with solid tumors that has returned after a period of improvement or does not respond to treatment, including central nervous system tumors. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

PRIMARY OBJECTIVES:

I. To estimate the maximum-tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of trebananib (AMG 386) administered as a weekly intravenous infusion to children with recurrent or refractory solid tumors.

II. To determine the tolerability of the solid tumor MTD and/or RP2D of AMG 386 in children with central nervous system (CNS) tumors.

III. To define and describe the toxicities of AMG 386 administered on this schedule.

IV. To characterize the pharmacokinetics and immunogenicity of AMG 386 in children with refractory cancer.

V. To measure changes in vascular permeability relative to baseline, evaluated by magnetic resonance imaging (MRI) perfusion, following AMG 386 administration in pediatric patients with CNS tumors.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of AMG 386 within the confines of a Phase 1 study.

II. To measure biologic markers of angiogenesis with potential for correlation with disease response.

OUTLINE: This is a dose-escalation study (part 1) followed by a safety and imaging study (part 2).

Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 to 6 months for up to 1 year.

Tipo de estudio

Intervencionista

Inscripción (Actual)

37

Fase

  • Fase 1

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

  • Canadá
    • Ontario
      • Toronto, Ontario, Canadá, M5G 1X8
        • Hospital for Sick Children
  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35233
        • University of Alabama at Birmingham Cancer Center
      • Birmingham, Alabama, Estados Unidos, 35233
        • Children's Hospital of Alabama
    • California
      • Orange, California, Estados Unidos, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, Estados Unidos, 94143
        • UCSF Medical Center-Parnassus
    • District of Columbia
      • Washington, District of Columbia, Estados Unidos, 20010
        • Children's National Medical Center
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Children's Healthcare of Atlanta - Egleston
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60611
        • Lurie Children's Hospital-Chicago
    • Indiana
      • Indianapolis, Indiana, Estados Unidos, 46202
        • Riley Hospital for Children
    • Michigan
      • Ann Arbor, Michigan, Estados Unidos, 48109
        • C S Mott Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55455
        • University of Minnesota/Masonic Cancer Center
    • Missouri
      • Saint Louis, Missouri, Estados Unidos, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, Estados Unidos, 10032
        • Columbia University/Herbert Irving Cancer Center
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45229
        • Cincinnati Children's Hospital Medical Center
    • Oregon
      • Portland, Oregon, Estados Unidos, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
        • Childrens Oncology Group
      • Pittsburgh, Pennsylvania, Estados Unidos, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Tennessee
      • Memphis, Tennessee, Estados Unidos, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • Washington
      • Seattle, Washington, Estados Unidos, 98105
        • Seattle Children's Hospital
    • Wisconsin
      • Milwaukee, Wisconsin, Estados Unidos, 53226
        • Children¿s Hospital of Wisconsin

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

2 años a 21 años (Niño, Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Part 1: Patients must have had histologic verification of non-CNS solid tumor malignancy at original diagnosis or relapse
  • Part 2: Patients must have had histologic verification of CNS malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
  • Patients must have either measurable or evaluable disease
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16 years of age; Note: neurologic deficits in patients with CNS tumors (Part 2 of the study) must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy

    • Myelosuppressive chemotherapy: at least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
    • Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
    • Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
    • Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
    • Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
    • Radiation therapy (XRT): at least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
    • Stem cell infusion without TBI: no evidence of active graft vs host disease and at least 56 days must have elapsed after transplant or stem cell infusion
  • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment
  • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the required blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions)

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 mg/dL (6 to < 10 years of age)
    • 1.2 mg/dL (10 to < 13 years of age)
    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
  • Urine protein: =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1,000 mg in a 24-hour urine sample
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by gated radionuclide study
  • No known cardiac disease
  • No history of myocardial infarction, severe or unstable angina, peripheral vascular disease or familial corrected QT (QTc) prolongation
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events version 4 [CTCAE v 4]) resulting from prior therapy must be =< grade 2
  • For Part 2 only: No evidence of new CNS hemorrhage defined as more than punctate size and/or more than three foci of punctate hemorrhage on baseline magnetic resonance imaging (MRI) obtained within 14 days prior to study enrollment
  • No evidence of active bleeding
  • Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.2 x upper limit of normal (ULN) and an international normalized ratio (INR) =< 1.2
  • A blood pressure (BP) =< the 95th percentile for age, height, and gender, and not receiving medication for treatment of hypertension
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

  • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study participation, and for 6 months after completion of AMG 386 administration
  • Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anticancer agents are not eligible
  • Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
  • Patients who are currently receiving therapeutic anticoagulation with heparin, low-molecular weight heparin, or Coumadin are not eligible for this trial
  • Patients who are currently receiving aspirin, ibuprofen, or other non-steroidal anti-inflammatory drugs or anti-platelet agents are not eligible
  • Patients who are receiving anti-hypertensive medications for control of blood pressure at the time of enrollment are not eligible for this trial
  • Patients who have an uncontrolled infection are not eligible
  • Patients who have received a prior solid organ transplantation are not eligible

  • Patients who have had or are planning to have the following invasive procedures are not eligible:

    • Major surgical procedure, laparoscopic procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment
    • Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g., Hickman or Broviac) and at least 7 days prior to enrollment for subcutaneous port
    • Core biopsy within 7 days prior to enrollment
    • Fine-needle aspirate within 7 days prior to enrollment
  • Patients with evidence of active bleeding: intratumoral hemorrhage by current imaging, or bleeding diathesis are not eligible
  • Patients with a history (within 365 days prior to study enrollment) of arterial/venous thromboembolic events including transient ischemic attack (TIA) or cerebrovascular accident (CVA) are not eligible
  • Patients with a history of hemoptysis within 42 days prior to study enrollment are not eligible
  • For Part 2: Patients with CNS tumors and evidence of new CNS hemorrhage of more than punctate size and/or more than three foci of punctate hemorrhage on baseline MRI obtained within 14 days prior to study enrollment are not eligible; Note: echocardiogram (ECHO) gradient MRI sequences per institutional guidelines are required for patients with CNS tumors
  • Patients who have a history of serious or non-healing wound, abdominal fistula, gastrointestinal ulcer or perforation, bone fracture, or intra-abdominal abscess within 28 days of study enrollment are not eligible
  • Patients with known cardiac or peripheral vascular disease are not eligible
  • Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible

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: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Treatment (trebananib)
Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Otro: Análisis de biomarcadores de laboratorio
Estudios correlativos
Otro: Estudio farmacológico
Estudios correlativos
Procedimiento: Imagen de resonancia magnética mejorada con contraste dinámico
Estudios correlativos
Otros nombres:
  • DCE-IRM
  • RM DCE
  • RM CON CONTRASTE DINÁMICO
Biológico: Trebananib
Dado IV
Otros nombres:
  • AMG 386
  • Angiopoyetina 1/2-Pepticuerpo neutralizante AMG 386

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of adverse events as assessed by the National Cancer Institute (NCI) CTCAE v 4.0
Periodo de tiempo: Up to 30 days after completion of study treatment
A descriptive summary of all toxicities will be reported.
Up to 30 days after completion of study treatment
MTD at which fewer than one-third of patients experience dose limiting toxicity as assessed by NCI CTCAE version 4.0
Periodo de tiempo: 28 days
28 days
Pharmacokinetic (PK) parameters of trebananib
Periodo de tiempo: At baseline, at days 1, 8, 15, and 22 of course 1
A descriptive analysis of PK parameters of trebananib will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
At baseline, at days 1, 8, 15, and 22 of course 1

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Changes in vascular permeability relative to baseline as evaluated by MRI in patients with CNS tumors
Periodo de tiempo: Baseline to up to 1 year
Baseline to up to 1 year
Disease response assessed according to RECIST version 1.1
Periodo de tiempo: Up to 1 year
Reported descriptively.
Up to 1 year

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Circulating antiangiogenic protein and Tie2 expressing monocyte levels
Periodo de tiempo: Up to 1 year
Reported descriptively and will utilize intra-patient variability estimated from two baseline blood samples.
Up to 1 year

Colaboradores e Investigadores

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

Patrocinador

National Cancer Institute (NCI)

Investigadores

  • Investigador principal: Sarah Leary, COG Phase I Consortium

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

1 de febrero de 2012

Finalización primaria (Actual)

1 de abril de 2016

Finalización del estudio (Actual)

1 de abril de 2016

Fechas de registro del estudio

Enviado por primera vez

19 de febrero de 2012

Primero enviado que cumplió con los criterios de control de calidad

19 de febrero de 2012

Publicado por primera vez (Estimar)

23 de febrero de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

3 de octubre de 2016

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

30 de septiembre de 2016

Última verificación

1 de septiembre de 2016

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • NCI-2012-00252 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
  • UM1CA097452 (Subvención/contrato del NIH de EE. UU.)
  • COG-ADVL1115
  • ADVL1115 (Otro identificador: CTEP)
  • PADVL1115_A05PAMDREVW01
  • CDR0000725371

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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