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Stereotactic Radiosurgery and Erlotinib in Treating Patients With Non-Small Cell Lung Cancer and Brain Metastases

2 de octubre de 2012 actualizado por: University of California, San Francisco

A Phase I Open-Label, Dose-Finding Study to Evaluate the Safety and Efficacy of Concurrent Radiosurgery and Erlotinib Administration in Non-Small Cell Lung Cancer Patients With Brain Metastases

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving erlotinib together with stereotactic radiosurgery may kill more tumor cells.

PURPOSE: This phase I clinical trial is studying the side effects of erlotinib when given together with stereotactic radiosurgery and to see how well it works in treating patients with non-small cell lung cancer with brain metastases.

Descripción general del estudio

Descripción detallada

OBJECTIVES:

Primary

  • To determine the acute as well as long-term toxicity (especially grade III neurotoxicity) of concurrent erlotinib hydrochloride and single-fraction radiosurgery in patients with non-small cell lung cancer (NSCLC) and brain metastases.

Secondary

  • To determine the freedom from progression in all detected lesions (i.e., radiosurgically treated and untreated) and the rate of response of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery as compared with historical controls treated with gamma knife radiosurgery alone at UCSF.
  • To measure the rate of freedom from any CNS progression in these patients at 1 year post treatment.
  • To assess cerebrospinal fluid (CSF) distribution of erlotinib hydrochloride by measuring both erlotinib hydrochloride and its major metabolite, OSI-420, in plasma and CSF at 4 or more days after initial erlotinib hydrochloride administration but before radiosurgery, and again at 4 weeks after stereotactic radiosurgery (optional).
  • To perform CSF and serum biomarker analysis for NSCLC using 2-dimensional liquid chromatography or mass spectrometry (2D-LC/MS).
  • To determine the incidence of subclinical leptomeningeal disease in patients assigned to gamma-knife treatment and who do not exhibit signs or symptoms or carcinomatous meningitis.

OUTLINE: Patients receive oral erlotinib hydrochloride once daily for at least 7 days. Patients then undergo stereotactic radiosurgery on day 0. Beginning the day after radiosurgery, patients receive erlotinib hydrochloride once daily for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients may continue to receive erlotinib hydrochloride at the discretion of their oncologist.

Patients undergo cerebrospinal fluid (CSF) and blood sample collection at baseline (at least 4 days after starting erlotinib hydrochloride and prior to radiosurgery) for pharmacokinetic and biomarker correlative studies. Samples are analyzed for concentrations of erlotinib hydrochloride by 2-dimensional-liquid chromatography/mass spectrometry and antithrombin by enzyme-linked immunosorbent assay.

After completion of study therapy, patients are followed every 3 months for 1 year.

Tipo de estudio

Intervencionista

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

    • California
      • San Francisco, California, Estados Unidos, 94115
        • UCSF Helen Diller Family Comprehensive Cancer 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

DISEASE CHARACTERISTICS:

  • Histologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria:

    • Fewer than 5 intraparenchymal brain metastases by gadolinium-enhanced MRI meeting the following criteria:

      • Maximum diameter ≤ 4.0 cm

        • If multiple lesions are present and one lesion is > 3.0 cm, the remaining lesions must be ≤ 3.0 cm in maximum diameter
      • No metastases within 3 mm of the optic nerve or optic chiasm such that some portion of the optic nerve or chiasm would receive > 9 Gy from radiosurgery
      • No metastases in the brainstem, midbrain, pons, or medulla
  • No prior complete resection of a single brain metastasis or of all known brain metastases

    • Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter
  • No clinical or radiographic evidence of unstable systemic progression (other than the study lesion[s]) within the past month

    • Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease
  • Isolated brain metastases with stable systemic disease allowed
  • No leptomeningeal metastases by MRI and/or positive cerebrospinal fluid cytology

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy ≥ 3 months
  • ANC > 1,000/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 10 g/dL
  • PT and PTT normal
  • AST < 2 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2 times ULN
  • Total bilirubin < 2 times ULN
  • Lactic dehydrogenase < 2 times ULN
  • Serum creatinine < 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study therapy
  • Neurologic function status 0-2
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride
  • No contraindication to MRI (e.g., cardiac pacemaker)
  • No absolute contraindication to lumbar puncture

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior systemic therapy allowed
  • No prior cranial radiotherapy

    • Prior radiotherapy to noncranial sites allowed
  • More than 1 week since prior intrathecal chemotherapy or prior treatment of leptomeningeal carcinoma
  • No concurrent systemic therapy

    • Prior or current erlotinib hydrochloride for treatment of systemic disease allowed provided systemic disease has not progressed while on erlotinib hydrochloride
  • No concurrent enzyme-inducing anticonvulsant

    • If patients are on an enzyme-inducing anticonvulsant (e.g., phenytoin, carbamazepine, or phenobarbital), the agent must be converted to a nonenzyme-inducing anticonvulsant before or at the start of erlotinib hydrochloride treatment
  • No concurrent CYP3A4 inhibitors or inducers (e.g., Hypericum perforatum [St. John wort] or ketoconazole)
  • No other concurrent investigational therapy

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)

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0.

Medidas de resultado secundarias

Medida de resultado
Enfermedad progresiva
Response rate of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery on this study vs the response rate of historical controls previously treated with gamma knife radiosurgery alone
CNS progression at 1 year
Distribution of erlotinib hydrochloride in plasma and cerebrospinal fluid (CSF)
CSF and serum biomarkers
Incidence of subclinical leptomeningeal disease

Colaboradores e Investigadores

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

Investigadores

  • Investigador principal: James L. Rubenstein, MD, PhD, University of California, San Francisco

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 enero de 2009

Finalización primaria (Actual)

1 de julio de 2009

Finalización del estudio (Actual)

1 de julio de 2009

Fechas de registro del estudio

Enviado por primera vez

19 de agosto de 2008

Primero enviado que cumplió con los criterios de control de calidad

19 de agosto de 2008

Publicado por primera vez (Estimar)

20 de agosto de 2008

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

4 de octubre de 2012

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

2 de octubre de 2012

Última verificación

1 de octubre de 2012

Más información

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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