- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01285037
A Study of LY2801653 in Advanced Cancer
A Phase 1 Study of LY2801653 in Patients With Advanced Cancer
Part A- The purpose of this study is to determine a safe dose of LY2801653 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2801653 in this participant population. Efficacy measures will be used to assess the activity of LY2801653.
Part B- The dose determined in Part A will be used along with efficacy measures to assess the activity of LY2801653 in participants with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma (HNSCC), uveal melanoma with liver metastasis, and cholangiocarcinoma.
Part C - the objective of Part C is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with HNSCC when taken with standard doses of cetuximab Part D - the objective of Part D is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with a standard dose of cisplatin.
Part E - the objective of Part E is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with gemcitabine plus cisplatin.
Part F - the objective of Part F is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with gastric cancer when taken with ramucirumab.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Arizona
-
Tucson, Arizona, Estados Unidos, 85724
- Arizona Cancer Center
-
-
District of Columbia
-
Washington, District of Columbia, Estados Unidos, 20007
- Georgetown University Medical Center
-
-
New York
-
New York, New York, Estados Unidos, 10029
- Mount Sinai Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Estados Unidos, 19111
- Fox Chase Cancer Center
-
Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University
-
Philadelphia, Pennsylvania, Estados Unidos, 19104
- University of Pennsylvania Hospital
-
-
Rhode Island
-
Providence, Rhode Island, Estados Unidos, 02903
- Rhode Island Hospital
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
- Part B- Diagnosed with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver with metastasis, or cholangiocarcinoma
- Part C - Diagnosed with head and neck squamous cell carcinoma and have received at least one prior platinum-based systemic therapy
- Part D - Diagnosed with cholangiocarcinoma and have not received more than 1 prior systemic therapy
- Part E - Diagnosed with cholangiocarcinoma, either intrahepatic or extrahepatic, that is unresectable, recurrent, or metastatic. Participants must not have received prior systemic front line therapy for metastatic or resectable disease (i.e. participants may have received adjuvant gemcitabine but have not yet received gemcitabine/cisplatin for recurrent metastatic disease). Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Participants should be evaluated for the need to undergo biliary drainage by stent placement prior to study participation. Participants should have adequate biliary drainage with no unresolved biliary obstruction.
- Part F - Histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma (participants with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ). Participants must be ramucirumab naïve. Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. human epidermal growth factor receptor 2 (HER2)/neu status should be documented, if known.
- Must be at least 18 years of age
- Adequate hematologic, renal, and liver functions
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Ability to swallow capsules, with the exception of head and neck squamous cell carcinoma participants who may have study drug crushed and administered through a feeding tube
Exclusion Criteria:
- Have serious preexisting medical conditions that would preclude participation in the study
- Have a chronic underlying infection
- Have symptomatic central nervous system (CNS) malignancy or metastasis
- Have current acute or chronic leukemia
- Are pregnant or lactating
- Have hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant
- Have a history of congestive heart failure with a New York Heart Association class greater than 2, unstable angina, recent myocardial infarction (within 6 months of study enrollment), transient ischemic attacks, stroke, or arterial or venous vascular disease
- Have a QTc interval greater than 470 msec
- For participants in Part B, C, D, E, and F, a tumor tissue sample is mandatory, when safe and feasible, for biomarker analysis
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: LY2801653
This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B). Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort. Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort. Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin. Part F consists of dose determination for LY2801653 in combination with ramicirumab. |
LY2801653 given orally once daily during 28-day cycles.
Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Cetuximab given via IV infusion once weekly, 400mg/m2 for first dose and 250mg /m2 for subsequent doses.
If LY2801653 treatment is stopped due to toxicity after a minimum of 4 cycles, cetuximab may be continued until disease progression.
In the event cetuximab treatment is stopped, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Cisplatin given via IV infusion once a week for 2 weeks and then every 3 weeks.
If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, cisplatin may be continued as monotherapy until progression of disease.
Participants discontinuing cisplatin therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit.
Gemcitabine given via IV infusion once a week for 2 weeks and then every 3 weeks.
If the LY2801653 is terminated for LY2801653-related toxicity after a minimum of 4 cycles, gemcitabine may be continued as monotherapy until progression of disease.
Participants discontinuing gemcitabine therapy may be allowed to continue single agent LY2801653 if they are receiving clinical benefit.
Otros nombres:
Ramucirumab given via IV infusion every 2 weeks in a 28-day treatment cycle.
Treatment with ramucirumab may continue until excessive toxicity or evidence of disease progression.
In the absence of disease progression, treatment with LY2801653 may continue even if ramucirumab is discontinued provided no dose limiting toxicity related to LY2801653 is present.
In the event that LY2801653 is discontinued, treatment with ramucirumab may be continued if there is no dose limiting toxicity related to ramucirumab.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Recommended dose for phase 2 studies: Maximum tolerated dose
Periodo de tiempo: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
Number of participants with tumor response
Periodo de tiempo: Part A: Baseline to study completion (estimated as 3 months)
|
Part A: Baseline to study completion (estimated as 3 months)
|
Clinical benefit rate (CBR)
Periodo de tiempo: Parts B, C, D: Baseline to study completion (estimated as 3 months)
|
Parts B, C, D: Baseline to study completion (estimated as 3 months)
|
Progression free survival (PFS)
Periodo de tiempo: Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
Duration of response
Periodo de tiempo: Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
Parts B, C, D: Baseline to study completion (estimated as up to 6 months)
|
Number of participants with clinically significant effects
Periodo de tiempo: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Pharmacokinetics: Area under the concentration/time curve (AUC)
Periodo de tiempo: Cycle 1, Day 1; Cycle 2, Day 1
|
Cycle 1, Day 1; Cycle 2, Day 1
|
Pharmacokinetics: Maximum plasma concentration (Cmax)
Periodo de tiempo: Cycle 1, Day 1; Cycle 2, Day 1
|
Cycle 1, Day 1; Cycle 2, Day 1
|
Maximum tolerated dose (MTD) of LY2801653 in combination with cetuximab for phase 2 studies in HNSCC
Periodo de tiempo: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Maximum tolerated dose (MTD) of LY2801653 in combination with cisplatin for phase 2 studies in cholangiocarcinoma
Periodo de tiempo: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Maximum tolerated dose (MTD) of LY2801653 in combination with gemcitabine plus cisplatin for phase 2 studies in cholangiocarcinoma
Periodo de tiempo: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Maximum tolerated dose (MTD) of LY2801653 in combination with ramucirumab for phase 2 studies in gastric carcinoma
Periodo de tiempo: Baseline to study completion (estimated as 3 months)
|
Baseline to study completion (estimated as 3 months)
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon - Fri 9AM to 5PM Eastern time (UTC/GMT - 5hours, EST), Eli Lilly and Company
Publicaciones y enlaces útiles
Publicaciones Generales
- He AR, Cohen RB, Denlinger CS, Sama A, Birnbaum A, Hwang J, Sato T, Lewis N, Mynderse M, Niland M, Giles J, Wallin J, Moser B, Zhang W, Walgren R, Plimack ER. First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer. Oncologist. 2019 Sep;24(9):e930-e942. doi: 10.1634/theoncologist.2018-0411. Epub 2019 Mar 4.
- Yan SB, Peek VL, Ajamie R, Buchanan SG, Graff JR, Heidler SA, Hui YH, Huss KL, Konicek BW, Manro JR, Shih C, Stewart JA, Stewart TR, Stout SL, Uhlik MT, Um SL, Wang Y, Wu W, Yan L, Yang WJ, Zhong B, Walgren RA. LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2013 Aug;31(4):833-44. doi: 10.1007/s10637-012-9912-9. Epub 2012 Dec 29.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos inmunológicos
- Gemcitabina
- Ramucirumab
- Cetuximab
Otros números de identificación del estudio
- 13008
- I3O-MC-JSBA (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. .
Ensayos clínicos sobre Cáncer
-
Abramson Cancer Center of the University of PennsylvaniaTerminadoPaciente con cancerEstados Unidos
-
Peking Union Medical College HospitalTerminadoEncuesta | Estado nutricional | Paciente con cancerPorcelana
-
Ankara Medipol UniversityReclutamientoCuidados personales | Inmunoterapia | Manejo de síntomas | Paciente con cancerPavo
-
Northwestern UniversityGenzyme, a Sanofi CompanyRetiradoCANCER DE PROSTATAEstados Unidos
-
Fundacao ChampalimaudTerminado
-
University College London HospitalsTerminado
-
GenSpera, Inc.RetiradoCancer de prostata.Estados Unidos
-
University of Colorado, DenverColorado State UniversityRetiradoRealidad virtual | Diagnóstico por imagen | Educación del paciente | Paciente con cancerEstados Unidos
-
Dana-Farber Cancer InstituteTerminadoCancer de RIÑON | Cancer de prostata | Cáncer genitourinarioEstados Unidos
-
Rabin Medical CenterReclutamiento
Ensayos clínicos sobre LY2801653
-
Eli Lilly and CompanyTerminado
-
Dana-Farber Cancer InstituteEli Lilly and CompanyTerminadoCarcinoma de pulmón de células no pequeñas | Tumor solidoEstados Unidos
-
Jacqueline Garcia, MDEli Lilly and CompanyTerminadoLeucemia mieloide aguda en adultos en recaída | Leucemia mieloide aguda refractaria en adultosEstados Unidos
-
Eli Lilly and CompanyTerminadoCáncer colonrectal | Linfoma de células del manto | Cáncer avanzadoEstados Unidos, Francia, Reino Unido
-
Eli Lilly and CompanyTerminadoLinfoma no Hodgkin | Tumor solido | Cáncer metastásico | Colangiocarcinoma | Cáncer avanzado | Carcinoma de vías biliares | Carcinoma de vesícula biliarJapón
-
Eli Lilly and CompanyActivo, no reclutandoCancer de pancreas | Tumor solido | Melanoma cutáneo | Tumores sólidos de alta inestabilidad de microsatélites (MSI-H) | Cáncer de mama (HR+HER2-)Francia, España, Bélgica, Corea, república de, Estados Unidos, Taiwán, Canadá
-
Eli Lilly and CompanyActivo, no reclutandoCáncer metastásico | Cáncer avanzado | Cáncer de vías biliaresEstados Unidos, Bélgica, España, Australia, Chequia, Dinamarca, Corea, república de, Taiwán, Alemania, Pavo, Francia, Reino Unido, Austria, Federación Rusa, México, Hungría, Argentina, Suecia