Dose Escalation Study of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
28 de junio de 2019 actualizado por: Millennium Pharmaceuticals, Inc.
A Phase I, Open Label, Dose Escalation Study of Oral Administration of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
This is a Phase I, open label, dose escalation study of oral administration of MLN0128 in combination with paclitaxel, with/without trastuzumab, in participants with advanced solid malignancies.
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
This is a Phase I, open-label study consisting of a dose escalation phase in advanced solid malignancies to determine the maximum tolerated dose (MTD) of oral administration of MLN0128 in 1 or more dosing schedules, combined with paclitaxel on Days 1, 8 and 15 of each cycle, followed by an expansion phase for further safety and preliminary efficacy.
Once the MTD is determined for each of the dosing schedules evaluated, a dose and schedule will be selected for the expansion phase, which may enroll participants into 2 arms in parallel:
- Arm A will consist of HER2- unknown cancer participants receiving MLN0128+paclitaxel
- Arm B will consist of HER2+ cancer participants receiving MLN0128+paclitaxel plus weekly trastuzumab
Tipo de estudio
Intervencionista
Inscripción (Actual)
68
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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Florida
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Fort Myers, Florida, Estados Unidos, 33905
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73104
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
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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:
- Voluntary written consent
- Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Ability to swallow oral medications
- For women of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to 30 days following the last study drug administration
- Male participants must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration
- Clinical laboratory values as specified in the protocol
- For expansion phase (Arm A) - HER2-/unknown participants will be enrolled
- For expansion phase (Arm B) - HER2+ cancer participants will be enrolled
Exclusion Criteria:
- Diagnosis of primary brain tumor
- Have received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug
- Known impaired cardiac function or clinically significant cardiac disease
- Known treatment with systemic corticosteroid within one week prior to the first administration of study drug
- Diabetes mellitus
- Human immunodeficiency virus (HIV) infection
- Known active cardiovascular disease condition as specified in protocol
- Pregnancy (positive serum or urine pregnancy test) or breast feeding
- Malabsorption due to prior gastrointestinal (GI) surgery, GI disease
- Other clinically significant co-morbidities
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons
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 |
|---|---|
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Experimental: MLN0128P 30 mg QW
MLN0128 and paclitaxel (MLN0128P): MLN0128 30 mg, capsule, orally, once weekly (QW) + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 40 mg QW
MLN0128 40 mg, capsule, orally, once a week (QW) + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 6 mg QD×3d QW
MLN0128 6 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 7 mg QD×3d QW
MLN0128 7 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 8 mg QD×3d QW
MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 9 mg QD×3d QW
MLN0128 9 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 10 mg QD×3d QW
MLN0128 10 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 7 mg QD×5d QW
MLN0128 7 mg, capsule, orally, once daily 5 days on/2 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128P 8 mg QD×3d QW HER2-
MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in human epidermal growth factor receptor 2 negative (HER-) cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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Experimental: MLN0128PH 8 mg QD×3d QW HER2+
MLN0128 + paclitaxel + trastuzumab (MLN0128PH): MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 plus trastuzumab 4 mg/kg loading dose on Day 1 followed by 2 mg/kg, intravenous each week of a 4-week cycle in HER+ cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
trastuzumab intravenous infusion
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Dose Escalation Phase: Maximum Tolerated Dose (MTD)
Periodo de tiempo: Cycle 1: Days 1 to 28
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MTD is the highest dose level at which the participants tolerate treatment without dose-limiting toxicities during the first cycle (28 days) of therapy.
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Cycle 1: Days 1 to 28
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Dose Escalation Phase: Number of Participants With at Least 1 Dose Limiting Toxicity (DLT)
Periodo de tiempo: Cycle 1: Days 1 to 28
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DLT was defined as any of the following occurring during Cycle 1 (Days 1-28) and attributable to MLN0128P: Grade ≥ 3 nonhematologic toxicity; Grade 3 thrombocytopenia with hemorrhage; Grade 4 neutropenia lasting > 7 days in the absence of growth factor support; Grade 4 neutropenia of any duration associated with fever 38.5 degrees C and/or infection; Any other Grade 4 hematologic toxicity; Inability to administer at least 75 % of doses of MLN0128 within Cycle 1 due to drug-related toxicity; Any clinically significant occurrence which the investigators and sponsor agree would place participants at undue safety risk; Participants who experienced an adverse event (AE) that met the definition for a DLT.
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Cycle 1: Days 1 to 28
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Objective Response Rate (ORR)
Periodo de tiempo: At screening and thereafter every 2 cycles of treatment until disease progression (Up to 65.8 weeks)
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ORR was defined as the percentage of participants with Complete Response (CR) and Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
Each cycle was a 28 day cycle.
CR was defined as the disappearance of all target lesions and for non-target lesions, the disappearance of all non-target lesions and normalization of tumor marker level.
PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions.
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At screening and thereafter every 2 cycles of treatment until disease progression (Up to 65.8 weeks)
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Percentage of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events(SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug
Periodo de tiempo: First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks)
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An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
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First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Cmax: Maximum Observed Plasma Concentration for MLN0128
Periodo de tiempo: Cycles 1 and 2: Day 1 or 2
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Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Cmin: Minimum Observed Plasma Concentration for MLN0128
Periodo de tiempo: Cycles 1 and 2: Day 1 or 2
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Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0128
Periodo de tiempo: Cycles 1 and 2: Day 1 or 2
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Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i.e., C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Terminal Phase Elimination Half-life (T1/2) for MLN0128
Periodo de tiempo: Cycle 1 Day 1
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Cycle 1 Day 1
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AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128
Periodo de tiempo: Cycle 1 Day 1
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Cycle 1 Day 1
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AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for MLN0128
Periodo de tiempo: Cycles 1 and 2: Day 1 or 2
|
Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Cmax: Maximum Observed Plasma Concentration for Paclitaxel
Periodo de tiempo: Cycles 1 and 2: Day 1
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Cycles 1 and 2: Day 1
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Cmin: Minimum Observed Plasma Concentration for Paclitaxel
Periodo de tiempo: Cycles 1 and 2: Day 1 or 2
|
Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
|
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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Paclitaxel
Periodo de tiempo: Cycles 1 and 2: Day 1
|
Cycles 1 and 2: Day 1
|
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Terminal Phase Elimination Half-life (T1/2) for Paclitaxel
Periodo de tiempo: Cycle 1 Day 1
|
Cycle 1 Day 1
|
|
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AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Paclitaxel
Periodo de tiempo: Cycle 1 Day 1
|
Cycle 1 Day 1
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AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for Paclitaxel
Periodo de tiempo: Cycle 1 Day 1
|
Cycle 1 Day 1
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AUC(0-24): Area Under the Plasma Concentration-time Curve Extrapolated to 24 Hours for Paclitaxel
Periodo de tiempo: Cycle 1 Day 1
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Cycle 1 Day 1
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CL: Total Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel
Periodo de tiempo: Cycle 1 Day 1
|
Cycle 1 Day 1
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Vss: Volume of Distribution at Steady State Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel
Periodo de tiempo: Cycle 1 Day 1
|
Cycle 1 Day 1
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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.
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)
28 de febrero de 2011
Finalización primaria (Actual)
15 de septiembre de 2017
Finalización del estudio (Actual)
15 de septiembre de 2017
Fechas de registro del estudio
Enviado por primera vez
21 de febrero de 2011
Primero enviado que cumplió con los criterios de control de calidad
9 de mayo de 2011
Publicado por primera vez (Estimar)
10 de mayo de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
8 de agosto de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
28 de junio de 2019
Última verificación
1 de junio de 2019
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Enfermedades hematológicas
- Neoplasias
- Neoplasias Hematológicas
- Mecanismos moleculares de acción farmacológica
- Agentes antineoplásicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Agentes antineoplásicos, fitogénicos
- Agentes antineoplásicos inmunológicos
- Paclitaxel
- Trastuzumab
Otros números de identificación del estudio
- INK128-003
- U1111-1181-8192 (Otro identificador: WHO)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach
for details).
To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias.
Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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. .