A Study of LY2875358 in Participants With Advanced Cancer
14 de febrero de 2017 actualizado por: Eli Lilly and Company
A Phase 1 Study of LY2875358 in Patients With Advanced Cancer
The objective of this study is to determine a recommended Phase 2 dose range of LY2875358 that may be safely administered to participants with advanced cancer.
In Part A and Part A2 of this study, escalating doses of LY2875358 as monotherapy and in combination with erlotinib will be evaluated for safety and tolerability, respectively.
Part B is a dose-confirmation segment for LY2875358 therapy in 5 different types of cancer: nonsquamous non-small cell lung cancer (NSCLC), castrate resistant prostate cancer (CRPC) with bone metastases, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), or uveal melanoma with liver metastases, and for LY2875358 in combination with trametinib in participants with uveal melanoma with liver metastases.
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
Protocol amendment (November, 2013) expanded Part B to study LY2875358 in combination with trametinib in participants with uveal melanoma with liver metastasis.
Tipo de estudio
Intervencionista
Inscripción (Anticipado)
117
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
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California
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La Jolla, California, Estados Unidos, 92037-0845
- University of California - San Diego
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Los Angeles, California, Estados Unidos, 90048-5615
- Cedars Sinai Medical Center
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San Francisco, California, Estados Unidos, 94115
- Univ of California San Francisco
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Santa Monica, California, Estados Unidos, 90404
- UCLA
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Mayo Clinic of Jacksonville
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109-0946
- University of Michigan
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55902
- Mayo Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University
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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:
- Part A: Have histological or cytological evidence of cancer (solid tumor, lymphoma, or multiple myeloma) that is advanced and/or metastatic and an appropriate candidate for experimental therapy
- Part A2: Histologic or cytologic diagnosis of advanced Non Small Cell Lung Cancer (NSCLC), Stage IIIB with malignant pleural effusion or Stage IV, completed at least 1 prior systemic regimen, and eligible for erlotinib therapy.
- Part B: Candidate for experimental therapy after standard therapies used or non-eligible for standard therapies. Histological or cytological evidence of 1 of the 5 tumor types:
Castrate-resistant prostate cancer (CRPC) with bone metastasis:
--Progressive Disease in the setting of castrate level of testosterone
Renal Cell Carcinoma (RCC):
--Histologic diagnosis of either clear-cell or papillary RCC (metastatic and unresectable, or bilateral, multifocal, unresectable RCC localized to kidneys).
NSCLC:
--Histologic or cytologic diagnosis of advanced NSCLC, Stage IIIB with malignant pleural effusion or Stage IV
Hepatocellular Carcinoma (HCC)
--Histologic or cytologic diagnosis of hepatocellular carcinoma
- Uveal Melanoma with liver metastasis
- Part A: Have the presence of measurable or nonmeasurable disease as defined by the RECIST v1.1 (Eisenhauer et al. 2009) or Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) or have measureable disease for multiple myeloma.
- Part A2 & B (RCC, NSCLC, HCC, and uveal melanoma): Have measurable disease as defined by RECIST v1.1.
- Give written informed consent prior to any study-specific procedures.
- Adequate organ function.
- Performance status of less than or equal to 2 on ECOG scale.
- Discontinued all previous cancer therapies, and any agents that have not received regulatory approval, for at least 21 days and recovered from the acute effects of therapy. Must have discontinued mitomycin-C or nitrosourea therapy for at least 42 days.
- Reliable and available for the duration of the study and willing to follow study procedures.
- Males and females (reproductive potential): Use medically approved contraceptive precautions during the study and for 4 months following the last dose of study drug.
- Females (childbearing potential): Have had a negative serum pregnancy test before the first dose of study drug and not be breast-feeding.
- Estimated life expectancy that will permit the participants to complete 8 weeks of treatment.
Exclusion Criteria:
- Serious preexisting medical conditions
- Symptomatic central nervous system malignancy or metastasis (screening not required).
- Acute or chronic leukemia.
- Active infection including HIV, hepatitis A, B or C
- Have second primary malignancy that may affect the interpretation of results.
- Have received a liver transplant, or have liver cirrhosis with a Child-Pugh Stage of B or C.
- Patients with active alcohol abuse, as determined by the treating investigator.
- Part A2: Unable to swallow tablets. Intolerant of therapy with erlotinib. Concomitant treatment with the cytochrome P450 3A (CYP3A) modulators. Must not have received treatment with any of these modulators within 14 days of study treatment.
- Have a history of New York Heart Association class ≥3, unstable angina, myocardial infarction 6 months prior to study drug
- QTc greater than 470 msec.
- Received previous treatment with any c-MET experimental therapeutic.
Part B Expansion Cohort 1 (CRPC):
- Increasing use of daily doses of opioid analgesics within 28 days prior to enrollment in the study.
- Neuroendocrine prostate cancer.
- Patients who have a solitary bone metastasis that has been irradiated are not eligible.
- Part B Expansion Cohort 6 (LY2875358 plus trametinib in participants with uveal melanoma with liver metastasis): Contra-indications for trametinib
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 de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: LY2875358
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Part A Dose escalation of LY2875358 administered intravenously (IV), Day 1 and 15 every 28 days for at least two cycles.
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Experimental: LY2875358 + erlotinib
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Part A2 Dose escalation of LY2875358 administered IV, on Day 1 and 15 every 28 days for at least two cycles in combination with daily erlotinib dosing (150 mg) taken orally (PO).
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Experimental: LY2875358 at Part A highest dose
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Part B (Dose Exploration): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles.
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Experimental: LY2875358 at Part A highest dose + trametinib
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Part B (in combination with trametinib): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles, in combination with trametinib at 2 mg orally once daily
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Recommended Phase 2 dose range of LY2875358 monotherapy and in combination with erlotinib
Periodo de tiempo: Baseline through Cycle 1
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Baseline through Cycle 1
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Pharmacokinetics: Maximum plasma concentration (Cmax)
Periodo de tiempo: Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Number of participants with a tumor response
Periodo de tiempo: Baseline to study completion (12 months)
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Baseline to study completion (12 months)
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Pharmacokinetics: Area under the concentration-time curve (AUC)
Periodo de tiempo: Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Time to progression and overall survival
Periodo de tiempo: Baseline to study completion (12 months)
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Baseline to study completion (12 months)
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Pharmacokinetics: Area under the concentration-time curve (AUC) of erlotinib or trametinib in combination with LY2875358
Periodo de tiempo: Cycle 1
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Cycle 1
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Change from baseline in Brief Pain Inventory (BPI) in Part B: Expansion Cohort 1
Periodo de tiempo: Baseline to study completion (12 months)
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Baseline to study completion (12 months)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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)
13 de abril de 2010
Finalización primaria (Actual)
8 de enero de 2015
Finalización del estudio (Actual)
26 de octubre de 2016
Fechas de registro del estudio
Enviado por primera vez
28 de enero de 2011
Primero enviado que cumplió con los criterios de control de calidad
31 de enero de 2011
Publicado por primera vez (Estimar)
1 de febrero de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
15 de febrero de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
14 de febrero de 2017
Última verificación
1 de febrero de 2017
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 13298
- I4C-MC-JTBA (Otro identificador: Eli Lilly and Company)
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. .