- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01085331
MEK Inhibitor MSC1936369B Plus FOLFIRI in Second Line K-Ras Mutated Metastatic Colorectal Cancer (mCRC)
A Double-blind, Randomized, Comparative, Multicenter, Exploratory, and Placebo-controlled Phase II Trial of FOLFIRI Plus MSC1936369B or Placebo With a Safety run-in Part as Second-line Treatment of Metastatic K Ras Mutated Colorectal Cancer Subjects
The research trial is testing the experimental treatment pimasertib (MSC1936369B) in combination with FOLFIRI, as second-line treatment in metastatic K Ras mutated colorectal cancer subjects. The study will be run in two parts:
Part 1, or Safety Run-in Part: Will determine the maximum tolerated dose and the recommended Phase 2 dose (RP2D) of pimasertib combined with FOLFIRI as second-line treatment in subjects with metastatic K Ras mutated colorectal cancer.
Part 2 or Phase 2 Randomised Part: Will assess the anti-tumor activity of pimasertib combined with FOLFIRI compared to FOLFIRI with placebo as second-line treatment in metastatic K Ras mutated colorectal cancer subjects.
Phase I which Is an open label dose escalation "3+3" cohort, non-randomized, safety Phase II which is a double blind randomized safety/efficacy
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
For Safety Run-in and Part 2 or Phase 2 Randomised Part
- Histologically confirmed K-Ras mutated colon/rectum cancer
- Subject's disease must have progressed during or after a first-line treatment for metastatic disease with oxaliplatin and fluoropyrimidines based chemotherapy with or without bevacizumab
- Evidence of metastatic measurable disease at trial entry as per Response Evaluation Criteria in Solid Tumors. Complete tumor assessment performed within 14 days prior to first trial drug administration
- Male/female subjects aged greater than or equal to (>=) 18 years
- Subject has read and understood the informed consent form
- Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Subjects and their partners must be willing to avoid pregnancy during the trial
Exclusion Criteria:
For Safety Run-in and Part 2 or Phase 2 Randomised Part
- Bone marrow impairment
- Renal impairment
- Liver function and liver cell integrity abnormality
- History of central nervous system (CNS) metastases
- History of difficulty of swallowing, malabsorption or other chronic gastrointestinal disease
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than (>)1
- Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B
- Has received extensive prior radiotherapy on more than 30 percent (%) of bone marrow reserves, or prior bone marrow/stem cell transplantation
- Has received chemotherapy, any investigational drug, or having participated in another clinical trial within the past 4 weeks prior to trial first drug administration
- Has a history of any other significant medical disease
- Past or current history (within the last 2 years prior to inclusion) of malignancies except for the indication under this study
- Has significant cardiac conduction abnormalities and/or pacemaker
- Is a pregnant or nursing female
- Has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion
- Other significant disease that in the Investigator's opinion would exclude the subject from the trial
- Known hypersensitivity to the trial treatment(s) or diluents (when applicable), including placebo or other comparator drug(s)
- Legal incapacity or limited legal capacity
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Part 1 or Safety Run-in Part: Pimasertib+FOLFIRI
|
Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.
Otros nombres:
Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter [mg/m^2] intravenous [i.v] infusion over 90 minutes or leucovorin [dl-leucovorin] 400 mg/m^2 i.v.
infusion over 90 minutes; followed by irinotecan 180 mg/m^2 given as a 90-minute infusion in 500 milliliter [mL] dextrose 5%; followed by a bolus 5-fluorouracil [FU] 400 mg/m^2 and a 46-hour infusion 5-FU 2400 mg/m^2) at conventional doses on days 1 and 15 of the same 28 day cycle.
|
Experimental: Part 2 or Phase 2 Randomized part: Pimasertib+FOLFIRI
Planned, not performed
|
Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.
Otros nombres:
Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter [mg/m^2] intravenous [i.v] infusion over 90 minutes or leucovorin [dl-leucovorin] 400 mg/m^2 i.v.
infusion over 90 minutes; followed by irinotecan 180 mg/m^2 given as a 90-minute infusion in 500 milliliter [mL] dextrose 5%; followed by a bolus 5-fluorouracil [FU] 400 mg/m^2 and a 46-hour infusion 5-FU 2400 mg/m^2) at conventional doses on days 1 and 15 of the same 28 day cycle.
|
Experimental: Part 2 or Phase 2 Randomized part: Placebo+FOLFIRI
Planned, not performed
|
Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter [mg/m^2] intravenous [i.v] infusion over 90 minutes or leucovorin [dl-leucovorin] 400 mg/m^2 i.v.
infusion over 90 minutes; followed by irinotecan 180 mg/m^2 given as a 90-minute infusion in 500 milliliter [mL] dextrose 5%; followed by a bolus 5-fluorouracil [FU] 400 mg/m^2 and a 46-hour infusion 5-FU 2400 mg/m^2) at conventional doses on days 1 and 15 of the same 28 day cycle.
Subjects will be administered with placebo orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Part 1 or Safety Run-in Part: Maximum Tolerated Dose (MTD)
Periodo de tiempo: Baseline up to Day 28 (Part 1)
|
MTD was defined as the dose level, at which the treatment-related dose limiting toxicity (DLT) occurred in >1 of 3 subjects or in >1 of 6 subjects.
DLT was defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Any Grade >=3 non-hematological toxicity except for Grade 4 asymptomatic increases in liver function tests (LFTs) reversible within 7 days in subjects with liver involvement, Grade 3 asymptomatic increases in LFTs reversible within 7 days in subjects without liver involvement, Grade 3 vomiting controlled with adequate and optimal therapy and prophylaxis, and Grade 3 diarrhea controlled with adequate and optimal anti-diarrhea therapy; any Grade 4 neutropenia lasing >5 days/ febrile neutropenia lasting >1 day; any Grade 4 thrombocytopenia/Grade 3 with bleeding; any treatment delay >2 weeks due to trial treatment-related adverse effects at any dose level and judged to be possibly or probably related to the trial treatment.
|
Baseline up to Day 28 (Part 1)
|
Part 2 or Phase 2 Randomised Part: Progression Free Survival (PFS)
Periodo de tiempo: From randomization up to first documented disease progression maximum up to 2 years
|
PFS was defined as time (in months) from the date of randomization to the first documentation of disease progression as reported and documented by the Investigator (i.e.
radiological progression per RECIST v1.0) or death for any cause.
|
From randomization up to first documented disease progression maximum up to 2 years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Part 1 or Safety Run-in Part: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
Periodo de tiempo: From the first dose of study drug administration up to 28 days after the last dose of study drug administration
|
An AE is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship.
An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
|
From the first dose of study drug administration up to 28 days after the last dose of study drug administration
|
Part 1 or Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Pimasertib, Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
|
Part 1 or Safety Run-in Part: Time to Reach Maximum Observed Concentration (Tmax) of Pimasertib, Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
|
Part 1 or Safety Run-in Part: Area Under the Concentration-time Curve From Time Zero to the Time of Last Observation (AUC0-t) of Pimasertib, Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Part 1 or Safety Run-in Part: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib, Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
The AUC(0-inf) of pimasertib and irinotecan was estimated by determining the total area under the concentration time curve extrapolated to infinity.
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Part 1 or Safety Run-in Part: Apparent Terminal Half Life (t1/2) of Pimasertib, Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
The t1/2 was defined as the time required for the plasma concentration of pimasertib and irinotecan to decrease 50% in the final stage of elimination.
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Part 1 or Safety Run-in Part: Apparent Oral Clearance (CL/f) of Pimasertib, (CL) Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Clearance of a drug was a measure of the rate at which drug was metabolized or eliminated by normal biological processes.
Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Part 1 or Safety Run-in Part: Apparent Oral Volume of Distribution (Vz f) Pimasertib, (Vz) of Irinotecan and SN-38
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration.
Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Part 1 or Safety Run-in Part: Ratio of Cmax for Pimasertib (Day 1/Day 8), Irinotecan and SN-38 (Day 1/Day 15)
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
|
|
Part 1 or Safety Run-in Part: Ratio of AUC0-inf of Pimasertib (Day 1/Day 8), Irinotecan and SN-38 (Day 1/Day 15)
Periodo de tiempo: Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan
|
The AUC(0-inf) was estimated by determining the total area under the concentration time curve extrapolated to infinity.
|
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan
|
Part 1 or Safety Run-in Part: Number of Subjects With Best Overall Response (BOR)
Periodo de tiempo: Up to 2 years
|
BOR was defined based on Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0) as following: Complete response (CR) was defined as the disappearance of all target and non-target lesions and no appearance of new lesions.
Partial response (PR) was defined as at least a 30 percent (%) decrease in the sum of the longest diameters (SLD) of the targeted lesions.
CR and PR had to be documented on 2 occasions separated by at least 4 weeks (28 days).
Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) being demonstrated during the first 4 weeks.
PD was defined as at least a 20% increase in the SLD of target lesions compared to the smallest SLD since the study treatment started.
|
Up to 2 years
|
Part 1 or Safety Run-in Part: Circulating Biomarkers in Serum
Periodo de tiempo: Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
|
Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
|
|
Part 2 or Phase 2 Randomized Part: Circulating Biomarkers
Periodo de tiempo: Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
|
Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
|
|
Part 2 or Phase 2 Randomized Part: Best Overall Response
Periodo de tiempo: Up to 2 years
|
BOR was defined based on Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST V1.0) as following: Complete response (CR) was defined as the disappearance of all target and non-target lesions and no appearance of new lesions.
Partial response (PR) was defined as at least a 30 percent (%) decrease in the sum of the longest diameters (SLD) of the targeted lesions.
CR and PR had to be documented on 2 occasions separated by at least 4 weeks (28 days).
Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) being demonstrated during the first 4 weeks.
PD was defined as at least a 20% increase in the SLD of target lesions compared to the smallest SLD since the study treatment started.
|
Up to 2 years
|
Part 2 or Phase 2 Randomized Part: Number of Subjects With TEAEs, Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
Periodo de tiempo: From the first dose of study drug administration up to 28 days after the last dose of study drug administration
|
An AE is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship.
An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
TEAES between first dose of study drug administration and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
|
From the first dose of study drug administration up to 28 days after the last dose of study drug administration
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Medical Responsible, Merck Serono S.A., Geneva
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
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 (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- EMR200066_004
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 colorrectal metastásico
-
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 Pimasertib
-
EMD SeronoSanofiTerminadoCáncer de ovariosEstados Unidos, Bélgica, Canadá, Australia, España, Francia, Polonia
-
Diakonhjemmet HospitalOslo University Hospital; University Hospital of North Norway; Helse Nord-Trøndelag... y otros colaboradoresReclutamientoEvento adverso relacionado con la inmunidadNoruega
-
EMD SeronoSanofiTerminadoMelanoma | Cáncer de mama | Cáncer colonrectal | Cáncer de pulmón de células no pequeñas | Tumor sólido metastásico | Tumor sólido localmente avanzadoEstados Unidos, Italia, España
-
EMD SeronoMerck KGaA, Darmstadt, GermanyTerminadoMelanoma cutáneo maligno metastásico o localmente avanzado con mutación N-RasEstados Unidos, Suecia, Australia, Francia, Italia, Sudáfrica, España, Reino Unido, Alemania, Países Bajos, Israel, Nueva Zelanda, Bélgica, Suiza
-
Merck KGaA, Darmstadt, GermanyMerck Serono Co., Ltd., JapanTerminado
-
BeiGeneActivo, no reclutandoCáncer de nasofaringe recurrente o metastásicoPorcelana, Taiwán, Tailandia
-
Merck KGaA, Darmstadt, GermanyMerck Serono S.A., GenevaTerminadoCáncer | Tumores sólidosFrancia, Bélgica, Australia, Países Bajos
-
Day One Biopharmaceuticals, Inc.ReclutamientoMelanoma | Cáncer colonrectal | Tumor solido | Cáncer de pulmón de células no pequeñas | Cáncer de vejiga | Cáncer De Tiroides Papilar | Astrocitoma pilocítico | Carcinoma urotelial de vejiga | Adenocarcinoma de células no pequeñas | Mutación MEK | Mutación RAS | Carcinoma acinar de páncreas | Mutación RAF | Amplificación... y otras condicionesEstados Unidos, Canadá, Corea, república de, España, Australia, Bélgica, Francia
-
EMD SeronoTerminadoLeucemia Mieloide Aguda | Neoplasias HematológicasEstados Unidos, Francia
-
Australian & New Zealand Children's Haematology...The Hospital for Sick Children; Kazia Therapeutics Limited; Day One Biopharmaceuticals... y otros colaboradoresAún no reclutandoCáncer infantil | Cáncer refractario | Cáncer recurrente | Tumor sólido infantil | Tumor cerebral infantilAustralia, Canadá