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Safety Study of Individual Paclitaxel Dose Adjustment Based on Pharmacokinetics in Non-Small Cell Lung Cancer (NSCLC)

6 de febrero de 2014 actualizado por: Caicun Zhou

Phase 3, Randomized, Open-label Study of the Safety of Individual Paclitaxel Dose Adjustment Based on Pharmacokinetic Follow up Versus Conventional Dosage in First-line Treatment in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Platinum-based doublets including paclitaxel, gemcitabine, or docetaxel are standard 1st regimens in Non-Small Cell Lung Cancer(NSCLC). The traditional method of individualizing cytotoxic drug dose is by using body surface area(BSA), which is not correlated with the ability of an individual to metabolize or excrete cytotoxic drugs, because it is not related to liver function and is poorly correlated with glomerular filtration rate, and does not seem to be a determinant of toxicity. Pharmacokinetic parameters such as area under the curve have been shown to correlate with toxicity. The advantages of using a fixed dose of antineoplastic agents for all of the patients are obvious. Pharmacokinetically guided treatment would avoid severe adverse effects, which has not been sufficiently investigated in advanced NSCLC.First, the investigators monitor the blood concentrations of paclitaxel and neutropenia blood toxicity after chemotherapy with paclitaxel and carboplatin in patients of NSCLC and verify suitable paclitaxel therapeutic window for Chinese patients. Then the investigators compare safety and efficacy between individual paclitaxel dose adjustment based on the therapeutic window compared with conventional dosage.

Descripción general del estudio

Descripción detallada

Primary end point: Common Terminology Criteria for Adverse Events(CTCAE) grade 4.

Secondary end point:Objective Response Rate(ORR),Progression Free Survival(PFS),Overall Survival(OS),Quality Of Life(QOL) etc.

Tipo de estudio

Intervencionista

Inscripción (Anticipado)

140

Fase

  • Fase 3

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

    • Shanghai
      • Shanghai, Shanghai, Porcelana, 200433
        • Reclutamiento
        • Medical Department, Shanghai Pulmonary Hospital
        • Sub-Investigador:
          • Jie Zhang, MD
        • Sub-Investigador:
          • Huiwei Qi, MD
        • Sub-Investigador:
          • Fengying Wu, MD

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 a 75 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

For inclusion in the study treatment period patients must fulfil all of the following criteria:

  1. Provision of informed consent.
  2. Male or female aged 18 years and over.
  3. Histologically or cytologically confirmed non-small cell lung carcinoma.
  4. Locally advanced Stage not amenable to local therapy (e.g. pleural effusion) or metastatic disease.
  5. No prior chemotherapy, biological (including targeted therapies such as Epidermal Growth Factor Receptor(EGFR) and Vascular Epidermal Growth Factor (VEGF) inhibitors) or immunological therapy. Patients who are willing to accept with paclitaxel and carboplatin as adjuvant chemotherapy will be eligible.
  6. World Health Organization (WHO) performance status (PS) of 0 to 2.
  7. Females of child-bearing potential must have negative serum pregnancy test. Sexually active males and females (of childbearing potential) willing to practice contraception during the study.
  8. Laboratory values within the range, as defined below, within two weeks of randomization:

    • Absolute neutrophils count(ANC)≥2.0×109/L
    • Platelets≥100×109/L
    • Serum bilirubin≤2×ULN; Aspartate transaminase(AST) and alanine tansaminase (ALT) ≤2.5×ULN(≤5×ULN if liver metastases)
    • Creatinine clearance≥60ml/min
  9. Measurable disease according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria with at least one measurable lesion not previously irradiated.
  10. Life expectancy ≥12 weeks.

Exclusion Criteria:

Any of the following is regarded as a criterion for exclusion from the study:

  1. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
  2. Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
  3. Known severe hypersensitivity to carboplatin, paclitaxel or any of the excipients of these products.Known severe hypersensitivity to pre-medications required for treatment with carboplatin / paclitaxel doublet chemotherapy.
  4. Prior treatment with paclitaxel.
  5. Current treatment with target drug and biological therapy.
  6. Pregnant or lactating woman.
  7. Prior chemotherapy, biological (including targeted therapies such as Epidermal Growth Factor Receptor(EGFR) and Vascular Epidermal Growth Factor (VEGF) inhibitors) or immunological therapy were received even if treatment was not paclitaxel and was completed in 4 weeks before day1 of study treatment.
  8. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
  9. Life expectancy of less than 12 weeks.
  10. Unable to tolerate carboplatin / paclitaxel doublet chemotherapy, as judged by the investigator.

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
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: pharmacokinetics group
Based on pharmacokinetics. Observe safety and efficacy. In first cycle a fixed Paclitaxel dose depends on BSA. In subsequent cycles the dosage of Paclitaxel will be adjusted depending on pharmacokinetics follow up .
Based on pharmacokinetics. Observe the toxicity in an individual patient after a fixed Paclitaxel dose depending on BSA and then the dosage of Paclitaxel is adjusted depending on pharmacokinetics follow up to avoid excess toxicity in subsequent cycles.
Based on body surface area. The dosage of Paclitaxel is based on the BSA of the patient. Paclitaxel/carboplatin up to 4 cycles or disease progression or intolerable toxicity.
Comparador activo: Body surface area(BSA) group
Based on body surface area. The dosage of Paclitaxel is based on the BSA of the patient. Paclitaxel/carboplatin up to 4 cycles or disease progression or intolerable toxicity.
Based on pharmacokinetics. Observe the toxicity in an individual patient after a fixed Paclitaxel dose depending on BSA and then the dosage of Paclitaxel is adjusted depending on pharmacokinetics follow up to avoid excess toxicity in subsequent cycles.
Based on body surface area. The dosage of Paclitaxel is based on the BSA of the patient. Paclitaxel/carboplatin up to 4 cycles or disease progression or intolerable toxicity.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
CTCAE grade 4 of the blood marrow
Periodo de tiempo: 24 months
Record the number of CTCAE grade 4 of the blood marrow such as Leukocytes, Neutrophils,Platelets and Hemoglobin in two treatment groups since the initiation of chemotherapy
24 months

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Objective response rate
Periodo de tiempo: Tumor assessment 6-8 weeks after the initiation of chemotherapy
The objective tumour response rate will be calculated as the percentage of evaluable patients with complete response (CR) and partial response (PR).
Tumor assessment 6-8 weeks after the initiation of chemotherapy
Progression free survival
Periodo de tiempo: 12 months
Progression Free Survival (PFS) is defined as the time from randomization to the first documentation of objective disease progression (PD) or death from any cause.
12 months
Overall survival
Periodo de tiempo: 24 months
Overall survival(OS) is defined as the interval between the date of randomization and the date of patient death due to any cause, or the last date the patient was known to be alive.
24 months
Quality of life
Periodo de tiempo: 24 months
Data on QoL will be assessed using the Functional Assessment of Cancer Therapy - Lung (FACT-L) for every patients.
24 months

Colaboradores e Investigadores

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

Patrocinador

Investigadores

  • Investigador principal: Caicun Zhou, Ph.D, Tongji University Affiliated Shanghai Pulmonary 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 enero de 2014

Finalización primaria (Anticipado)

1 de diciembre de 2015

Finalización del estudio (Anticipado)

1 de diciembre de 2016

Fechas de registro del estudio

Enviado por primera vez

27 de enero de 2014

Primero enviado que cumplió con los criterios de control de calidad

6 de febrero de 2014

Publicado por primera vez (Estimar)

10 de febrero de 2014

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

10 de febrero de 2014

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

6 de febrero de 2014

Última verificación

1 de febrero de 2014

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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