Dose Escalation Study of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
2019年6月28日 更新者：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.
調査の概要
詳細な説明
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
研究の種類
介入
入学 (実際)
68
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Florida
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Fort Myers、Florida、アメリカ、33905
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73104
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Tennessee
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Nashville、Tennessee、アメリカ、37203
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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実験的：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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実験的：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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実験的：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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実験的：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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実験的：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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実験的：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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実験的：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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実験的：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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実験的：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Dose Escalation Phase: Maximum Tolerated Dose (MTD)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Cmax: Maximum Observed Plasma Concentration for MLN0128
時間枠：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
時間枠：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
時間枠：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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Terminal Phase Elimination Half-life (T1/2) for MLN0128
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：Cycle 1 Day 1
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Cycle 1 Day 1
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2011年2月28日
一次修了 (実際)
2017年9月15日
研究の完了 (実際)
2017年9月15日
試験登録日
最初に提出
2011年2月21日
QC基準を満たした最初の提出物
2011年5月9日
最初の投稿 (見積もり)
2011年5月10日
学習記録の更新
投稿された最後の更新 (実際)
2019年8月8日
QC基準を満たした最後の更新が送信されました
2019年6月28日
最終確認日
2019年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- INK128-003
- U1111-1181-8192 (その他の識別子：WHO)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
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.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。