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Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

12 de mayo de 2017 actualizado por: Leora Horn, MD, Vanderbilt-Ingram Cancer Center

A Feasibility Study Investigating Translational Science in Chemotherapy-Naive Patients With Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Treated With the EGFR-TKI, Erlotinib

RATIONALE: Studying samples of tumor tissue, blood, and urine in the laboratory from patients receiving erlotinib may help doctors predict how patients will respond to treatment.

PURPOSE: The phase II trial is studying proteomic profiling to see how well it predicts response in patients receiving erlotinib for stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

OBJECTIVES:

Primary

  • To define a pre-treatment tumor proteomic profile that predicts response, stable disease, or progressive disease in patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer treated with erlotinib hydrochloride.

Secondary

  • To test and refine a pre-treatment serum proteomic expression pattern that predicts response to erlotinib hydrochloride and/or carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.
  • To test and refine tumor proteomic profiles that predict response to carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.
  • To analyze individual and pattern(s) of erlotinib hydrochloride-induced genomic and proteomic biomarker changes in relation to response or non-response to treatment.
  • To correlate the efficacy and toxicity of erlotinib hydrochloride with expression of EGFR, EGFR pathway, ErbB family, and other related biomarkers.
  • To determine a set of biomarkers to be evaluated in tumor tissue or surrogate tissues prior to treatment with erlotinib hydrochloride to enable patient selection for therapy.
  • To estimate response rate and progression-free and overall survival of patients treated with erlotinib hydrochloride as initial therapy.
  • To characterize the safety profile of erlotinib hydrochloride in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily until disease progression.

At the time of disease progression, patients receive standard chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Patients with non-squamous cell non-small cell lung cancer also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses.

Tumor tissue, plasma, serum, and urine samples are collected at baseline for proteomics analysis.

After the completion of study treatment, patients are followed every 8 weeks.

Tipo de estudio

Intervencionista

Inscripción (Actual)

116

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

  • Estados Unidos
    • Florida
      • Gainesville, Florida, Estados Unidos, 32610-0232
        • University of Florida Shands Cancer Center
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30308
        • Emory University
    • Michigan
      • Ann Arbor, Michigan, Estados Unidos, 48109-0942
        • University of Michigan Comprehensive Cancer Center
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37232-6838
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, Estados Unidos, 37064
        • Vanderbilt-Ingram Cancer Center - Cool Springs
      • Nashville, Tennessee, Estados Unidos, 37064
        • Vanderbilt-Ingram Cancer Center at Franklin
    • Texas
      • Houston, Texas, Estados Unidos, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas

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 120 años (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 1 of the following criteria:

    • Stage IIIB (with pleural effusion) or stage IV disease
    • Recurrent disease after prior surgery
  • Measurable or evaluable disease is desirable but not required

  • No untreated symptomatic brain metastases

    • Patients who are neurologically unstable despite radiotherapy for the brain metastases are not eligible
    • No requirement for steroids to control neurological symptoms

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mm³
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 2.0 mg/dL
  • Total bilirubin ≤ 1.5 mg/dL
  • Normal hemostasis by history
  • PT/PTT within 0.5 seconds of normal range
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to undergo biopsy procedures
  • No known severe hypersensitivity to erlotinib hydrochloride or any of the excipients of this product
  • No other concurrent malignancies or malignancies diagnosed within the past 5 years, except basal cell carcinoma or cervical cancer in situ

  • No significant cardiac disease, including any of the following:

    • NYHA class III or IV heart disease
    • Uncontrolled dysrhythmia
    • Myocardial infarction within the past 6 months

  • No evidence of clinically active interstitial lung disease

    • Chronic stable radiographic changes that are asymptomatic allowed
  • No evidence of any other severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
  • No evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial

  • No uncontrolled hypertension

    • Blood pressure must be ≤ 150/90 mmHg on a stable antihypertensive regimen

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 6 months since prior adjuvant chemotherapy
  • No unresolved chronic toxicity > CTC grade 2 from prior anticancer therapy (except alopecia)
  • More than 30 days since prior non-approved or investigational drugs
  • No prior chemotherapy for advanced NSCLC
  • No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or St. John's wort
  • No concurrent administration of other drugs known to inhibit EGFR
  • No other concurrent anti-neoplastic or anti-tumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
  • No other concurrent investigational agents
  • Concurrent cardioprotective doses of aspirin, as recommended by the physician, for cardiovascular disease allowed

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
Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression.
Otro: análisis de biomarcadores de laboratorio
Recolección de sangre y tejidos.
Droga: bevacizumab
15 mg/m2 given through a vein for every 3 weeks
Droga: carboplatin
AUC = 6 given through a vein on day 1 of each cycle.
Droga: erlotinib hydrochloride
150 mg taken by mouth daily
Droga: paclitaxel
200 mg/m2 given through a vein on day 1 of each cycle.
Genético: gene expression analysis
Blood and tissue collection.
Genético: protein expression analysis
Blood and tissue collection.
Genético: proteomic profiling
Blood and tissue collection.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease
Periodo de tiempo: End of treatment date
End of treatment date

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pre-treatment Serum Proteomic Expression Pattern as a Predictor of Response to Erlotinib Hydrochloride and/or Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
Periodo de tiempo: End of treatment date
End of treatment date
Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride
Periodo de tiempo: End of treatment date
End of treatment date
Analysis of Individual and Pattern(s) of Erlotinib Hydrochloride-induced Genomic and Proteomic Biomarker Changes in Relation to Response or Non-response to Treatment
Periodo de tiempo: End of treatment date
End of treatment date
End of treatment date
Correlation of the Efficacy and Toxicity of Erlotinib Hydrochloride With Expression of EGFR, EGFR Pathway, ErbB Family, and Other Related Biomarkers
Periodo de tiempo: End of treatment date
End of treatment date
Determination of a Set of Biomarkers to be Evaluated in Tumor Tissue or Surrogate Tissues Prior to Treatment With Erlotinib Hydrochloride to Enable Patient Selection for Therapy
Periodo de tiempo: End of treatment date
End of treatment date
Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
Periodo de tiempo: Through study completion, an average of 1 year
Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. The response rate is calculated as the percentage of PR+CR among patients assessed for response.
Through study completion, an average of 1 year
Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
Periodo de tiempo: Through study completion, an average of 1 year
PFS is defined as the time from on erlotinib treatment date to progression or death (whichever comes first) before cross-over to PC or PC+B. For those did not progressed nor died, they were censored at the last follow up (either the off erlotinib treatment date or lost follow up date). The median survival time and 95% confidence interval were estimated using Kaplan-meier method.
Through study completion, an average of 1 year
Number of Patients With Worst-grade Toxicities Per Grade
Periodo de tiempo: Through study completion, an average of 1 year

The intensity of the AE will be graded according to the Common Toxicity Criteria (CTC) of the (US) National Cancer Institute (NCI) - Cancer Therapy Evaluation Program (CTEP) [version 3.0 of December 2003] (Appendix B).

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Through study completion, an average of 1 year
Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
Periodo de tiempo: Through study completion, an average of 1 year
The overall survival time is defined as the time from on treatment to death. Patients were censored of they were alive at the last follow up date. The median survival time and its confidence interval were estimated using Kaplan-meier method.
Through study completion, an average of 1 year

Colaboradores e Investigadores

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

Patrocinador

Vanderbilt-Ingram Cancer Center

Colaboradores

National Cancer Institute (NCI)

Investigadores

  • Silla de estudio: David Carbone, M.D., Ph.D., Vanderbilt-Ingram Cancer Center

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 octubre de 2007

Finalización primaria (Actual)

1 de septiembre de 2011

Finalización del estudio (Actual)

1 de diciembre de 2013

Fechas de registro del estudio

Enviado por primera vez

26 de octubre de 2007

Primero enviado que cumplió con los criterios de control de calidad

26 de octubre de 2007

Publicado por primera vez (Estimar)

30 de octubre de 2007

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de junio de 2017

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

12 de mayo de 2017

Última verificación

1 de mayo de 2017

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • VICC-THO-0640
  • P30CA068485 (Subvención/contrato del NIH de EE. UU.)
  • VU-VICC-THO-0640
  • VU-VICC-070494

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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