Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

BI 6727 (Volasertib) in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumour

21 de agosto de 2018 actualizado por: Boehringer Ingelheim

A Phase I Dose Escalation Trial of BI 6727 in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumors

The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events when combined with a platinum therapy (cisplatin or carboplatin).

Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727 combination treatment with cisplatin and carboplatin.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

61

Fase

  • Fase 1

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

  • Bélgica
      • Bruxelles, Bélgica
        • 1230.6.3201 Boehringer Ingelheim Investigational Site
      • Leuven, Bélgica
        • 1230.6.3202 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. Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
  2. Indication for a treatment with platinum therapy as judged by the investigator
  3. Age 18 years or older
  4. Written informed consent consistent with ICH-GCP and local legislation
  5. ECOG performance score lower or equal 2
  6. Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapies (except alopecia grade 2)

Exclusion criteria:

  1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
  2. Pregnancy or breastfeeding
  3. Active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV I/II
  4. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
  5. Second malignancy currently requiring another anti-cancer therapy
  6. ANC less than 1500 / mm3
  7. Platelet count less than 100 000 / mm3
  8. Bilirubin greater than 1.5 mg / dl (> 26 micromol / L, SI unit equivalent) (except Gilbert's syndrome)
  9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
  10. Serum creatinine greater than 1.5 mg / dl (> 132 micromol / L, SI unit equivalent) or creatinine clearance <70ml/min (as calculated according to Cockcroft-Gault formula for GFR estimate)
  11. Known history of relevant QT-prolongation, e.g. long QT-syndrome
  12. Pre-existing clinically relevant hearing loss
  13. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  14. Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks before start of therapy or concomitantly with this trial
  15. Systemic anti-cancer therapy or radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
  16. Patients unable to comply with the protocol
  17. Active alcohol or drug abuse

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: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: A. BI 6727-cisplatin
patient to receive 3-weekly infusion escalating dose of BI 6727 combined to cisplatin
Droga: BI 6727
low to high dose
Experimental: B. BI 6727-carboplatin
patient to receive 3-weekly infusion escalating dose of BI 6727 combined to carboplatin
Droga: BI-6727
Low to high dose (administered every 3 weeks). Depending on the toxicities observed, intermediary dose levels may be added

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Maximum Tolerated Dose
Periodo de tiempo: 3 weeks

The maximum tolerated dose (MTD) was defined as the highest dose studied for which the incidence of DLT was less than 33% (i.e. 1/6 patients) during the first cycle, for Volasertib in combination with cisplatin or carboplatin.

0=not maximum tolerated dose, 1=was maximum tolerated dose.
3 weeks

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of Participants With Dose Limiting Toxicities
Periodo de tiempo: 3 weeks
Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle.
3 weeks
Objective Response Rate
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Objective response was defined as the proportion of participants having at least a best response of complete response (CR) or partial response (PR) determined based on RECIST criteria, version 1.0 (V1.0).

Tumour response was documented using appropriate techniques
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Duration of Objective Response
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Duration of objective response was defined as the time from first documented confirmed complete response (CR) or partial response (PR) to first evidence of progressive disease (PD) or death from any cause, whichever occurred first, determined based on RECIST V1.0 criteria.

Tumour response was documented using appropriate techniques
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Best Overall Response
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Best overall response was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria.
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Disease Control Rate
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Percentage of participants with confirmed disease control, defined as the proportion of patients with a best overall response of at least stable disease (SD), determined based on RECIST V1.0 criteria.
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Duration of Disease Control
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Duration of Disease control was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first.
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Progression-free Survival
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Progression-free survival based on RECIST V1.0 criteria was defined as the time from start of treatment to the date of evidence of progressive disease (PD) or death from any cause, whichever occurred first.
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Incidence and Intensity of Adverse Events According to CTCAE Version 3.0
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Incidence and intensity of adverse events according to common terminology criteria for adverse events (CTCAE) version 3.0
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Percentage of Participants With Serious Adverse Events
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Percentage of participants with serious adverse events (AEs)
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Percentage of Participants With Significant Adverse Events
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Percentage of participants with significant adverse events (AEs): dose limiting toxicity (DLT) was defined as significant AE.

DLTs (i.e. significant AEs) per protocol were:

  • drug related CTCAE grade 3 or 4 non haematological toxicity (except vomiting or diarrhoea responding to supportive treatment and ototoxicity)
  • drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection
  • drug related CTCAE Grade 4 thrombocytopenia
  • drug related febrile neutropenia grade 3 (ANC<1000/mm³ and fever≥ 38.5°C)
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Total Plasma Clearance After Intravascular Administration (CL)
Periodo de tiempo: 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion
Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.
1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion
Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)
Periodo de tiempo: 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion
Apparent volume of distribution at steady state following intravascular administration (Vss) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.
1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion
Change From Baseline in Pulse Rate
Periodo de tiempo: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Change from baseline in pulse rate at last value on treatment
Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Change From Baseline in Neutrophils
Periodo de tiempo: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Change from baseline in neutrophils with the maximum value on treatment
Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Change From Baseline in Platelets
Periodo de tiempo: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Change from baseline in platelets with the maximum value on treatment
Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Neutrophils
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of participants (%) with possible clinically significant abnormalities for neutrophils: : defined as neutrophils >=CTCAE grade 2 (CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Platelets
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Frequency of participants (%) with possible clinically significant abnormalities for platelets : defined as platelets >=CTCAE grade 2 (based on CTCAE v3.0), with worsening from baseline.

The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Last Value on Treatment
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on last value on treatment.

Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Last Value on Treatment
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on last value on treatment.

Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Worst Value on Treatment
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on worst value on treatment.

Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Worst Value on Treatment
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on worst value on treatment.

Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Worst CTCAE Grade on Treatment for Platelets
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Worst CTCAE Grade on Treatment for Neutrophils
Periodo de tiempo: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).
From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days

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 agosto de 2009

Finalización primaria (Actual)

1 de noviembre de 2011

Finalización del estudio (Actual)

1 de febrero de 2012

Fechas de registro del estudio

Enviado por primera vez

31 de agosto de 2009

Primero enviado que cumplió con los criterios de control de calidad

31 de agosto de 2009

Publicado por primera vez (Estimar)

1 de septiembre de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

31 de enero de 2019

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

21 de agosto de 2018

Última verificación

1 de agosto de 2018

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • 1230.6
  • 2008-003926-40 (Número EudraCT: EudraCT)

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. .

Suscribir