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Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC

28 de julio de 2016 actualizado por: Boehringer Ingelheim

A Randomised Open-label Phase II Trial of BI 6727 Monotherapy and BI 6727 in Combination With Standard Dose Pemetrexed Compared to Pemetrexed Monotherapy in Second Line Non-small Cell Lung Cancer

The trial objective will be to evaluate whether BI 6727 monotherapy or in combination with pemetrexed may be effective in the treatment of advanced or metastatic NSCLC in patients who relapsed after or failed first-line platinum based therapy.

The secondary objectives are to identify the acceptable dose of BI 6727 in combination with pemetrexed and to characterize the pharmacokinetic profiles of BI 6727 alone. Arm A, BI6727 monotherapy arm is closed to further recruitment.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

143

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

  • Bahamas
      • Nassau, Bahamas
        • 1230.5.00118 Boehringer Ingelheim Investigational Site
  • Canadá
    • Alberta
      • Edmonton, Alberta, Canadá
        • 1230.5.00104 Boehringer Ingelheim Investigational Site
    • British Columbia
      • Kelowna, British Columbia, Canadá
        • 1230.5.00114 Boehringer Ingelheim Investigational Site
      • Surrey, British Columbia, Canadá
        • 1230.5.00109 Boehringer Ingelheim Investigational Site
      • Vancouver, British Columbia, Canadá
        • 1230.5.00107 Boehringer Ingelheim Investigational Site
    • Ontario
      • Hamilton, Ontario, Canadá
        • 1230.5.00105 Boehringer Ingelheim Investigational Site
      • Kitchener, Ontario, Canadá
        • 1230.5.00119 Boehringer Ingelheim Investigational Site
      • Oshawa, Ontario, Canadá
        • 1230.5.00116 Boehringer Ingelheim Investigational Site
      • Ottawa, Ontario, Canadá
        • 1230.5.00108 Boehringer Ingelheim Investigational Site
      • Toronto, Ontario, Canadá
        • 1230.5.00110 Boehringer Ingelheim Investigational Site
    • Quebec
      • Montreal, Quebec, Canadá
        • 1230.5.00102 Boehringer Ingelheim Investigational Site
      • Montreal, Quebec, Canadá
        • 1230.5.00106 Boehringer Ingelheim Investigational Site

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:

  1. Pathologic or cytologic confirmed diagnosis of NSCLC
  2. Recurrent, advanced or metastatic NSCLC that has progressed following one prior platinum based chemotherapy regimen (not counting adjuvant or neoadjuvant chemotherapy if completed more than 12 months prior to platinum based therapy)
  3. Patients who are eligible for pemetrexed as second line chemotherapy
  4. Measurable disease by one or more techniques (CT, MRI) according to RECIST
  5. Patients aged 18 years or older
  6. Life expectancy of at least three (3) months
  7. Eastern Cooperative Oncology Group (ECOG) performance Score 0-2
  8. Written informed consent that is consistent with ICH-GCP guidelines and local legislation

Exclusion criteria:

  1. Treatment with an investigational drug in another clinical study within the past 28 days prior to the start of therapy or concomitantly with this study
  2. Anti-cancer therapy for NSCLC (except radiotherapy for palliative reasons) within the past 28 days prior to Treatment Day 1 of Cycle 1 of this trial
  3. Any persisting toxicities which are deemed to be clinically significant from the previous therapy
  4. Patients who have received more than one prior chemotherapy regimen for advanced disease (not including prior adjuvant therapy). Patients may have received prior epidermal growth factor receptor tyrosine kinase inhibitors.
  5. Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
  6. Active brain metastases (stable for <28 days, symptomatic, or requiring concurrent steroids). Patients who have received prior whole brain irradiation and whose brain metastases are stable according to the criteria above will not be excluded.
  7. Other active malignancy diagnosed within the past 3 years (other than non melanomatous skin cancer and cervical intraepithelial neoplasia)
  8. Concomitant intercurrent illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with trial requirement or which are considered relevant for the evaluation of the efficacy or safety of the trial drug
  9. Patients unable or unwilling to interrupt concomitant administration of NSAIDS 5 days prior to, the day of and 2 days after the administration of pemetrexed, with the exception of lose dose aspirin 81mg daily
  10. Patients who have received prior therapy with pemetrexed
  11. Absolute neutrophil count (ANC) less than 1,500/mm3
  12. Platelet count less than 100,000/mm3
  13. Hemoglobin <90g/L
  14. Total bilirubin >26µmol/L
  15. Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) less than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
  16. Serum creatinine level >133µmol/L and/or creatinine clearance (measured or calculated) <45 ml/min
  17. Clinically relevant QTc prolongation
  18. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  19. Pregnancy or breast feeding
  20. Known or suspected active alcohol or drug abuse
  21. Patients unable to comply with the protocol
  22. Any known hypersensitivity to the trial drugs or their excipients
  23. Patients with NSCLC of confirmed Squamous histology

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: BI 6727 +pemetrexed
BI 6727 plus 500 mg/^m2 pemetrexed i.v. on day 1 of 21 day cycle
Droga: pemetrexed
500 mg/m^2 i.v. on day 1 of 21 day cycle
Droga: BI 6727
BI 6727 i.v. on day 1 of a 21 day cycle
Comparador activo: pemetrexed
500 mg/m^2 i.v. on day 1 of a 21 day cycle
Droga: pemetrexed
500 mg/m^2 i.v. on day 1 of 21 day cycle

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First.
Periodo de tiempo: From randomization until disease progression or death

Disease progression was defined according to the Response Evaluation Criteria in Solid Tumours (RECIST)) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occured first. For patients with known date of progression (or death): PFS [days] = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS [days, censored] = date of last imaging showing no progression - date randomization + 1 day.

The number of participants analysed displays the number of patients with an event (progression).
From randomization until disease progression or death

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria.
Periodo de tiempo: From first drug infusion until 21 days after last drug infusion, up to 1100 days
Objective tumor response, defined as complete response (CR), and partial response (PR), evaluated according to RECIST criteria. Evaluation of target lesions: Complete Response (CR): disappearance of all target lesions. Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Evaluation of nontarget lesions: Complete Response (CR): disappearance of all nontarget lesions.
From first drug infusion until 21 days after last drug infusion, up to 1100 days
Overall Survival (OS)
Periodo de tiempo: From randomization until time of death
Overall survival (OS) was defined as the duration of time from randomization to time of death.
From randomization until time of death
Duration of Overall Response
Periodo de tiempo: From the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented
The duration of overall response was measured from the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded since treatment began). The duration of overall CR was measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. Duration of disease control is presented here.
From the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented
Occurrence and Intensity of AEs Graded According to CTCAE.
Periodo de tiempo: From first drug infusion until 21 days after last drug infusion, up to 1100 days
All patients were carefully monitored during and after each treatment cycle. Adverse events (AEs) were recorded and were graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE).
From first drug infusion until 21 days after last drug infusion, up to 1100 days
Occurence of DLT
Periodo de tiempo: Patients were treated for repeated 21-day treatment cycles until disease progression or intolerability of the trial drug, whichever occurred first.

Occurence of Dose-limiting toxicity (DLT). A DLT was defined as one or more of the following:

  • treatment-related CTCAE Grade 3 or 4 nonhematological toxicity (except emesis or diarrhea responding to supportive treatment).
  • treatment-related CTCAE Grade 4 neutropenia for ≥7 days and/or complicated by infection.
  • CTCAE Grade 4 thrombocytopenia.
Patients were treated for repeated 21-day treatment cycles until disease progression or intolerability of the trial drug, whichever occurred first.
Frequency of Patients With Possible Clinically Significant Abnormalities
Periodo de tiempo: From first drug infusion until 21 days after last drug infusion, up to 1100 days
Frequency of patients with possible clinically significant abnormalities
From first drug infusion until 21 days after last drug infusion, up to 1100 days
Cmax of Volasertib
Periodo de tiempo: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion
Cmax - maximum measured concentration of volasertib in plasma.
5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion
Total Clearance (CL) of Volasertib
Periodo de tiempo: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion
CL - total clearance of volasertib in plasma after IV administration
5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion
Vss of Volasertib
Periodo de tiempo: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion
Vss - apparent volume of distribution at steady state following IV administration of volasertib
5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion
Cmax of Pemetrexed
Periodo de tiempo: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion
Cmax - maximum measured concentration of pemetrexed in plasma
5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion
CL of Pemetrexed
Periodo de tiempo: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion
CL - total clearance of pemetrexed in plasma after IV administration
5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion
Vss of Pemetrexed
Periodo de tiempo: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion
Vss - apparent volume of distribution at steady state following IV administration of pemetrexed
5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion

Colaboradores e Investigadores

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

Patrocinador

Boehringer Ingelheim

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.

Publicaciones Generales

Enlaces Útiles

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 septiembre de 2012

Finalización del estudio (Actual)

1 de agosto de 2015

Fechas de registro del estudio

Enviado por primera vez

15 de enero de 2009

Primero enviado que cumplió con los criterios de control de calidad

15 de enero de 2009

Publicado por primera vez (Estimar)

16 de enero de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

20 de septiembre de 2016

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

28 de julio de 2016

Última verificación

1 de julio de 2016

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 1230.5

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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