Dose Escalation Study of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
28. června 2019 aktualizováno: 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.
Přehled studie
Postavení
Dokončeno
Intervence / Léčba
Detailní popis
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
Typ studie
Intervenční
Zápis (Aktuální)
68
Fáze
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Florida
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Fort Myers, Florida, Spojené státy, 33905
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Oklahoma
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Oklahoma City, Oklahoma, Spojené státy, 73104
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Tennessee
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Nashville, Tennessee, Spojené státy, 37203
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Dose Escalation Phase: Maximum Tolerated Dose (MTD)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Cmax: Maximum Observed Plasma Concentration for MLN0128
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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, 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
Časové okno: 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
Časové okno: 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 Paclitaxel
Časové okno: Cycles 1 and 2: Day 1
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Cycles 1 and 2: Day 1
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Terminal Phase Elimination Half-life (T1/2) for Paclitaxel
Časové okno: 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 Paclitaxel
Časové okno: 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 Paclitaxel
Časové okno: Cycle 1 Day 1
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Cycle 1 Day 1
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AUC(0-24): Area Under the Plasma Concentration-time Curve Extrapolated to 24 Hours for Paclitaxel
Časové okno: 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
Časové okno: Cycle 1 Day 1
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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
Časové okno: Cycle 1 Day 1
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Cycle 1 Day 1
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
28. února 2011
Primární dokončení (Aktuální)
15. září 2017
Dokončení studie (Aktuální)
15. září 2017
Termíny zápisu do studia
První předloženo
21. února 2011
První předloženo, které splnilo kritéria kontroly kvality
9. května 2011
První zveřejněno (Odhad)
10. května 2011
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
8. srpna 2019
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
28. června 2019
Naposledy ověřeno
1. června 2019
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary podle místa
- Hematologická onemocnění
- Novotvary
- Hematologické novotvary
- Molekulární mechanismy farmakologického působení
- Antineoplastická činidla
- Tubulinové modulátory
- Antimitotické látky
- Modulátory mitózy
- Antineoplastické látky, fytogenní
- Antineoplastická činidla, Imunologická
- Paklitaxel
- Trastuzumab
Další identifikační čísla studie
- INK128-003
- U1111-1181-8192 (Jiný identifikátor: WHO)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu 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.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ano
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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