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Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)

8 de enero de 2013 actualizado por: Proacta, Incorporated

A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer

The current understanding of PR104 justifies the evaluation of PR104 with docetaxel in subjects with Non Small Cell Lung Cancer (NSCLC). These include:

  • Aldo-keto reductase 1C3 (AKR1C3). NSCLC has been shown to express high levels of AKR1C3 in about one half of tumors tested. Subjects with high levels of AKR1C3 should have increased activation of PR104 within their tumor.
  • Hypoxia. NSCLC has been demonstrated to be a tumor with hypoxia based on both direct tumor measurements (oxygen electrodes) and hypoxic positron emission tomography (PET) imaging. Tumor hypoxia in NSCLC should be sufficient to activate PR104 to its active metabolites PR104H and PR104M.
  • Preclinical data. The use of docetaxel and PR104 alone and in combination in preclinical models demonstrates activity of PR104 as a single agent and supraadditive activity when PR104 and docetaxel are used in combination.
  • Manageable toxicity. PR104 and docetaxel with Granulocyte Colony-stimulating Factor (G-CSF) have been combined in a prior phase I study. A Maximum Tolerated Dose (MTD) has been identified and the major toxicities of this combination are understood.

The current study will provide an estimate of the activity of PR104 in subjects with NSCLC. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity in NSCLC to warrant a larger phase III registration study in this indication.

Primary objectives

• Estimate the response rate (RR) of PR104/docetaxel

Secondary objectives

  • Evaluate survival
  • Evaluate progression free survival (PFS)
  • Evaluate time to progression (TTP)
  • Evaluate safety
  • Evaluate the pharmacokinetics of PR104 and its metabolites
  • Evaluate the pharmacokinetics of docetaxel
  • Evaluate the tumor hypoxia using 18F-fluoromisonidazole (18F-MISO) PET imaging
  • Collect diagnostic biopsy samples for the determination of AKR1C3
  • Collect plasma samples for assessment of potential biomarkers of tumor hypoxia

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

A randomized phase II, multi-center, open-label, study of docetaxel versus docetaxel/PR104.

Following informed consent, subjects will undergo baseline evaluation with history, physical exams, blood work and disease assessment. Selected subjects will undergo PET imaging with F18 fluoromisonidazole (F18-FMISO) and Fludeoxyglucose (FDG) for assessment of hypoxia and glucose metabolism, and pharmacokinetics of PR104.

Subjects will be randomized between arm 1 consisting of docetaxel, 75 mg/m^2, administered intravenously (IV), every 21 days (an approved dose and schedule) and arm 2 consisting of docetaxel, 60 mg/m^2 with PR104 at 770 mg/m^2, IV, every 21 days. Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF. One cycle will be 21 days in duration. Subjects will be evaluated weekly. A disease assessment will be performed every six weeks. Subjects with progression will be removed from study. Subjects with a response or stable disease may continue on study if this is considered beneficial by their physician.

Tipo de estudio

Intervencionista

Inscripción (Actual)

42

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

  • Canadá
    • Quebec
      • Montreal, Quebec, Canadá, H2W 1S6
        • McGill University
  • Estados Unidos
    • California
      • San Diego, California, Estados Unidos, 92123
        • Sharp Clinical Oncology Research
    • Florida
      • Miami, Florida, Estados Unidos, 33136
        • University of Miami/Sylvester Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60611
        • Northwestern University
      • Skokie, Illinois, Estados Unidos, 60076
        • Orchard Research, LLC
      • Zion, Illinois, Estados Unidos, 60099
        • Midwestern Regional Medical Center
    • Indiana
      • Beech Grove, Indiana, Estados Unidos, 46107
        • St. Francis Health Services
    • Iowa
      • Ames, Iowa, Estados Unidos, 50010
        • McFarland Clinic/William R. Bliss Cancer Center
      • Cedar Rapids, Iowa, Estados Unidos, 52402
        • Iowa Blood & Cancer Care
    • Kansas
      • Wichita, Kansas, Estados Unidos, 67214
        • Cancer Center of Kansas
    • Kentucky
      • Mt. Sterling, Kentucky, Estados Unidos, 40353
        • Montgomery Cancer Center
    • Louisiana
      • Baton Rouge, Louisiana, Estados Unidos, 70809
        • Baton Rouge General/Penington
    • Maryland
      • Annapolis, Maryland, Estados Unidos, 21401
        • Annapolis Oncology Center
      • Baltimore, Maryland, Estados Unidos, 21215
        • Lapidus Cancer Center/Sinai Hospital
    • Michigan
      • Kalamazoo, Michigan, Estados Unidos, 49048
        • Kalamazoo Hematology & Oncology
    • Nevada
      • Reno, Nevada, Estados Unidos, 89502
        • VA Sierra Nevada Health Care System
    • North Carolina
      • Durham, North Carolina, Estados Unidos
        • VA Medical Center
      • Winston-Salem, North Carolina, Estados Unidos, 27103
        • Piedmont Hematology Oncology Associates, PLLC
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45220
        • Cincinnati VA Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos
        • University of Pennsylvania
    • South Carolina
      • Columbia, South Carolina, Estados Unidos, 29209
        • WJB Dorn VA Medical Center
    • Tennessee
      • Memphis, Tennessee, Estados Unidos, 38120
        • ACORN
    • Texas
      • Dallas, Texas, Estados Unidos, 75246
        • Mary Crowley Medical Research Center
      • Fort Worth, Texas, Estados Unidos, 76104
        • The Center for Cancer and Blood Disorders
      • Midland, Texas, Estados Unidos, 79701
        • Texas Oncology - Allison Cancer Center
      • Temple, Texas, Estados Unidos, 76508
        • Scott & White Memorial Hospital
  • Nueva Zelanda
      • Hamilton, Nueva Zelanda
        • Waikato District Health Board

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

Inclusion Criteria:

  • Subjects with locally advanced or metastatic NSCLC (stage IIIb/IV) who have relapsed following adjuvant or first line therapy with a platinum containing regimen, and are appropriate candidates for treatment with single agent docetaxel
  • Confirmed NSCLC by prior pathological analysis (tissue aspirate or biopsy)
  • At least 21 days from prior chemotherapy
  • At least 30 days from prior irradiation therapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy of 12 weeks or more
  • Adequate hematologic function [Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; platelet count ≥100x10^9/L; hemoglobin ≥8.5 g /dL maintained in the absence of red blood cell transfusions; and prothrombin time international normalized ratio ≤1.7; or prothrombin time ≤2 seconds above control)
  • Adequate hepatic function (albumin ≥2.8 g/dL; total bilirubin ≤2 mg/dL [51.3 μmol/L]; and alanine aminotransferase and aspartate aminotransferase ≤1.5 times the upper limit of the normal range)
  • Adequate renal function (serum creatinine ≤2.0 times the upper limit of the normal range or creatinine clearance ≥60 mL/min).
  • At least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)

Exclusion Criteria:

  • Previous treatment with docetaxel (prior treatment with paclitaxel permitted)
  • Receipt of more than one prior systemic chemotherapy regimen
  • Active concomitant malignancy likely to effect any of the primary or secondary outcome measures in the current study
  • Women who are pregnant, breast-feeding or planning to become pregnant during the study
  • Men or women of reproductive-potential who are unwilling to use an effective method of contraception during the study and for 30 days following the last dose
  • Evidence of a significant medical disorder or laboratory finding that, in the opinion of the Investigator, compromises the subject's safety during study participation
  • Active Central Nervous System (CNS) metastatic disease requiring intervention
  • Less than 4 weeks since major surgery
  • Known human immunodeficiency virus (HIV) positivity

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
Comparador activo: Docetaxel 75 mg/m^2
Subjects randomized to the docetaxel arm will be administered 75 mg/m^2, IV, every 21 days (an approved dose and schedule)
Droga: docetaxel
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Otros nombres:
  • Taxotere
Droga: docetaxel
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Otros nombres:
  • Taxotere
Experimental: PR104 + 60 mg/m^2 docetaxel
Subjects randomized to the PR104/docetaxel arm will be administered 60 mg/m^2 docetaxel, IV, every 21 days plus 770 mg/m^2 PR104, IV, every 21 days and prophylactic G-CSF.
Droga: docetaxel
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Otros nombres:
  • Taxotere
Droga: docetaxel
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Otros nombres:
  • Taxotere
Droga: PR104
770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Droga: Granulocyte colony-stimulating factor
Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops.
Otros nombres:
  • G-CSF
  • GCSF

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Periodo de tiempo: Participants were followed for the duration on study, an average of 4 months
Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Participants were followed for the duration on study, an average of 4 months

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Safety and Tolerability: Serious Adverse Events
Periodo de tiempo: 30 days following last administration of study treatment
The number of participants with at least one Serious Adverse Event was measured.
30 days following last administration of study treatment
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
Periodo de tiempo: Within 1 year of enrollment

AKR1C3 was evaluated on a semi-quantitative scale, and the percentage of cells staining at each of the following four levels was recorded: 0 (unstained), 1+ (weak staining), 2+ (moderate staining) and 3+ (strong staining).

Patients with a strong staining score (3+) were considered to be AKR1C3 positive
Within 1 year of enrollment

Colaboradores e Investigadores

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

Patrocinador

Proacta, Incorporated

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 marzo de 2009

Finalización primaria (Actual)

1 de enero de 2010

Finalización del estudio (Actual)

1 de mayo de 2010

Fechas de registro del estudio

Enviado por primera vez

12 de marzo de 2009

Primero enviado que cumplió con los criterios de control de calidad

13 de marzo de 2009

Publicado por primera vez (Estimar)

16 de marzo de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

10 de enero de 2013

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

8 de enero de 2013

Última verificación

1 de enero de 2013

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • PR104-2003

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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