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Crizotinib Efficacy In Non-Small Cell Lung Cancer Patients With Anaplastic Lymphoma Kinase Translocation

20 de julio de 2016 actualizado por: National Taiwan University Hospital

An Exploratory Study Of Crizotinib Efficacy In Non-Small Cell Lung Cancer Patients With Anaplastic Lymphoma Kinase Translocation Determined By Different Molecular Diagnostic Methods

This is an exploratory study in patients with locally advanced or metastatic Non-small cell lung cancer. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods.

Descripción general del estudio

Descripción detallada

This is an exploratory non-randomized study in patients with locally advanced or metastatic NSCLC. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods. Patients who failed and progressed through at least one line of platinum containing chemotherapy and who are older than 70 years old with failure of chemotherapy will be eligible for this study. We will screen EML4-ALK fusion gene by RT-PCR (HotSart Taq Master Mix Kits, Qiaqen) from patients' malignant pleural effusions and the detail was described in previous study[1]. We will also use IHC analyses (5A4 monoclonal antibody, Novocastra) to screen ALK protein expression in patients' FFPE tumor sections. We will further do FISH analysis by using commercial Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe (2p23) (Abott Molecular Inc., Des Plaines, IL) to detect ALK rearrangement in positive screening tumors. Samples are deemed to be FISH-positive if more than 15% of 50 scored tumor cells had split ALK 5' and 3' probe signals or had isolated 3' signals[5]. Patients who have ALK rearrangement determined in any of 3 molecular analyses methods and apply for crizotinib will receive 250mg of crizotinib twice daily until disease progression, unacceptable toxicities or the withdrawal of consent is noted.

Patients will be monitored carefully for the development of adverse experiences. Adverse experiences will be evaluated according to criteria outlined in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients will also be monitored for clinical and/or radiographic evidence of disease progression according to RECIST 1.1.

The primary endpoint of the study is overall response rate in patients with positive ALK determined from different molecular analysis methods. The secondary endpoint included overall response in specific subsets of patients, progression-free survival (PFS), and overall survival (OS) at 1 year. PFS is defined as the time from day 1 of crizotinib to disease progression or patient's death. OS was defined as the time from day 1 of crizotinib treatment to patient's death.

During the treatment, patients will have safety measurements performed at specified time points. Disease response will be assessed during the study by radiographic (e.g., CT or MRI), and clinical (e.g., physical examination) evaluations, if applicable. Overall tumor response will be assessed at the designated time points (every 12 weeks, using Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1). The crizotinib treatment could be continued after RECIST-defined disease progression if clinical benefit is still noted by primary physician.

Tipo de estudio

De observación

Inscripción (Actual)

12

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

      • Taipei, Taiwán, 100
        • Department of Oncology, National Taiwan University Hospital

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

20 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra no probabilística

Población de estudio

Patients with locally advanced or metastatic NSCLC who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods.

Descripción

Inclusion Criteria:

  1. Patient must have locally advanced or metastatic NSCLC (Stage IIIb or Stage IV by AJCC 7th.) with positive ALK determined by RT-PCR or IHC (5A4, 3+ score). Patients must have failed and progressed through at least one line of platinum containing chemotherapy or failed and progressed through chemotherapy if they were older than 70 years old.
  2. Patient must have at least one measurable lesion.
  3. Patient is male or female and ≥ 20 years of age on the day of signing informed consent.
  4. Patient must have performance status ≤ 2 on the ECOG Performance Scale.
  5. Patient must have adequate organ function as indicated by the following laboratory values: adequate liver (total bilirubin < 1.5 x the upper limit of normal (ULN), total bilirubin > 1.5 x ULN but biliary obstruction is documented radiologically, transaminases < 2.5 x ULN or < 5 x ULN if due to liver metastases), renal (creatinine < 2 x ULN) and bone marrow function (hemoglobin > 8g/dL, absolute neutrophil count > 1 X 109/L and platelets > 30 X 109/L)
  6. Female patient of childbearing potential has a negative serum or urine pregnancy test β-hCG within 5 days prior to receiving the first dose of study medication.
  7. Patients have completed chemotherapy regimens have residual toxicity < Grade 1 except alopecia.
  8. Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
  9. Patient is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.

Exclusion Criteria:

  1. Patient who has had chemotherapy within 2 weeks prior to Day 1 of Cycle 1 or has not recovered from the adverse events due to previous agents prior to Day 1 of Cycle 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1 except alopecia.
  2. Patient who has had major surgery within 4 weeks prior to starting of treatment or expect major surgery in the study duration. Patient who has had prior radiotherapy (except brain) within 1 week prior to Day 1 of Cycle 1.
  3. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study.
  4. Patient has known active CNS metastases and/or carcinomatous meningitis unless patients were clinically stable for 2 weeks after radiotherapy.
  5. Patient with a primary central nervous system tumor.
  6. Patient has known hypersensitivity to the components of study drug or its analogs.
  7. Patient has severe systemic disease.
  8. Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  9. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  10. Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
  11. Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  12. Patient is known to be Human Immunodeficiency Virus (HIV)-positive
  13. Patient currently has active Hepatitis B which is defined as patient has positive serum HBsAg with ALT > 2 x ULN and HBV DNA > 20,000 IU/mL.

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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Overall response rate in patients with positive ALK determined from different molecular analysis methods.
Periodo de tiempo: It is defined as the time from day 1 of crizotinib to disease progression or patient's death.
It is defined as the time from day 1 of crizotinib to disease progression or patient's death.

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Supervivencia libre de progresión (PFS)
Periodo de tiempo: 1 año
1 año
Supervivencia global (SG)
Periodo de tiempo: 1 año
1 año

Colaboradores e Investigadores

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

Investigadores

  • Investigador principal: James Chih-Hsin Yang, MD, PhD, National Taiwan University Hospital

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.

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 junio de 2012

Finalización primaria (Anticipado)

1 de diciembre de 2016

Finalización del estudio (Anticipado)

1 de marzo de 2017

Fechas de registro del estudio

Enviado por primera vez

28 de junio de 2012

Primero enviado que cumplió con los criterios de control de calidad

10 de julio de 2012

Publicado por primera vez (Estimar)

11 de julio de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

21 de julio de 2016

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

20 de julio de 2016

Última verificación

1 de julio de 2016

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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