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Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-FU or Cisplatin and Capecitabine

24 de octubre de 2018 actualizado por: ASLAN Pharmaceuticals

Phase I Study to Evaluate the Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-Fluorouracil or Cisplatin and Capecitabine

This is a phase IB study to assess the safety and tolerability of ASLAN001 when given in combination with either Cisplatin and 5-Fluorouracil or Cisplatin and Capecitabine, with a view to identifying the recommended Phase II dose.

Descripción general del estudio

Descripción detallada

This is an open-label, Phase I, dose escalation study of ASLAN001 given in combination with Regimen A or Regimen B, in patients with metastatic solid tumors, eligible to receive the cisplatin/5-fluorouracil or cisplatin/capecitabine regimen.

Dose of ASLAN001 starts from 400mg BID; then, dose escalation to 500mg BID or dose de-escalation to 300mg BID will depend on DLTs observed in cohort.

Regimen A: Depends on preferred medical practice, Cohort 1A will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and 5 fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks; or will receive ASLAN001 400 mg BID in combination with Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks.

Regimen B: Cohort 1B will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and oral capecitabine 1,000 mg/m2 BID for 14 days every 3 weeks.

Tipo de estudio

Intervencionista

Inscripción (Actual)

31

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

      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Taipei, Taiwán, 100
        • National Taiwan University Hospital
      • Taipei, Taiwán, 112
        • Taipei Veterans General Hospital

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

20 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Male or female patients 20 years of age or older at the time written informed consent is obtained.
  2. Regimen A: Patients with metastatic solid tumors eligible for treatment with cisplatin and 5-fluorouracil. The standard dose and schedule of cisplatin and 5-fluorouracil will be according to the preference of investigators and institutions.

    Regimen B: Patients with metastatic solid tumors eligible for treatment with cisplatin in combination with capecitabine.

  3. Patients with a partial gastrectomy may be allowed to participate in the study as long as they can take oral medications and meet all other inclusion/exclusion criteria.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to enrolment:

Hematological function, as follows:

  • Absolute neutrophil count ≥ 1.5 x 109/L.
  • Platelet count ≥ 100 x 109/L.
  • Hemoglobin ≥ 9 g/dL.

Coagulation function, as follows:

  • Partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
  • International normalized ratio ≤ 1.5.

Renal function, as follows:

• Creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault formula.

Hepatic function, as follows:

  • Total bilirubin ≤ 1.5 x ULN.
  • AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present).

Exclusion Criteria:

  1. Patients with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy.
  2. Patients receiving proton pump inhibitors or H2 antagonists for established, symptomatic gastro duodenal ulceration or gastroesophageal reflux disease.
  3. Patients with unresolved toxicities of grade 2 or more from prior anti-cancer therapies.
  4. Untreated or symptomatic central nervous system metastases. Patients with a history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the patient is clinically stable and is off corticosteroids for at least 2 weeks prior to enrolment.
  5. Major surgical procedures within 28 days prior to enrolment.
  6. Clinically significant cardiovascular diseases that are symptomatic or uncontrolled.
  7. Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
  8. Pregnant or breast-feeding females.
  9. Patients who have hearing impairment, due to the potential for ototoxicity of cisplatin.
  10. Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the patient or the validity of the study results

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: Regimen A / Amended Regimen A

Regimen A: Cisplatin + 5-fluorouracil

ASLAN001 daily in combination with:

Cisplatin 80 mg/m2 IV infusion for 1 day and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks for up to 6 cycles.

Or

Amended Regimen A: Cisplatin + 5-fluorouracil + leucovorin

ASLAN001 daily in combination with:

Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks for up to 6 cycles.

ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Otros nombres:
  • Varlitinib
  • ARRY-334543

Cisplatin 80 mg/m2 IV infusion and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks;

Or

Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks.

Experimental: Regimen B

Regimen B: Cisplatin + capecitabine

ASLAN001 daily in combination with:

Cisplatin 60-80 mg/m2 IV infusion on Day 1 and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks for up to 6 cycles.

ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Otros nombres:
  • Varlitinib
  • ARRY-334543
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Safety and Tolerability of ASALN001
Periodo de tiempo: First 2 cycles

Safety and tolerability as evaluated with:

DLTs (in first 2 cycles); Maximum tolerated dose (MTD) of ASLAN001 in combination with cisplatin/capecitabine or cisplatin/5-FU will be determined.

First 2 cycles
Safety and Tolerability of ASALN001
Periodo de tiempo: Baseline to post-dose

Safety and tolerability as evaluated with:

Adverse events.

Baseline to post-dose

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Preliminary assessment of the efficacy
Periodo de tiempo: Along the study duration
•To provide a preliminary assessment of the efficacy of ASLAN001 when given in combination in Regimen A or Regimen B as measured by the objective response rate (ORR).
Along the study duration
Pharmacokinetics profile (AUC) of ASLAN001
Periodo de tiempo: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 6 hours (AUC0-6).
Along the study duration
Pharmacokinetics profile (Cmax) of ASLAN001
Periodo de tiempo: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax).
Along the study duration
Pharmacokinetics profile (Cmin) of ASLAN001
Periodo de tiempo: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to minimum (trough) plasma concentration (Cmin).
Along the study duration
Pharmacokinetics profile (RacAUC0-6) of ASLAN001
Periodo de tiempo: Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B.
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to accumulation ratio for AUC (RacAUC0-6).
Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B.
Pharmacokinetics profile (Tmax) of ASLAN001
Periodo de tiempo: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with
Along the study duration

Colaboradores e Investigadores

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

Patrocinador

Investigadores

  • Silla de estudio: ASLAN Pharma, ASLAN Pharmaceuticals

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 (Actual)

5 de agosto de 2014

Finalización primaria (Actual)

12 de junio de 2017

Finalización del estudio (Actual)

15 de septiembre de 2017

Fechas de registro del estudio

Enviado por primera vez

21 de junio de 2015

Primero enviado que cumplió con los criterios de control de calidad

5 de enero de 2016

Publicado por primera vez (Estimar)

7 de enero de 2016

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

25 de octubre de 2018

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

24 de octubre de 2018

Última verificación

1 de octubre de 2018

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. .

Ensayos clínicos sobre Tumor solido

Ensayos clínicos sobre ASLAN001

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