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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1181-8192 | Other Identifier | WHO |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MLN0128P 30 mg QW | Experimental | 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. |
|
| MLN0128P 40 mg QW | Experimental | 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. |
|
| MLN0128P 6 mg QD×3d QW | Experimental | 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. |
|
| MLN0128P 7 mg QD×3d QW | Experimental | 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. |
|
| MLN0128P 8 mg QD×3d QW | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MLN0128 | Drug | MLN0128 capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation Phase: Maximum Tolerated Dose (MTD) | MTD is the highest dose level at which the participants tolerate treatment without dose-limiting toxicities during the first cycle (28 days) of therapy. | Cycle 1: Days 1 to 28 |
| Dose Escalation Phase: Number of Participants With at Least 1 Dose Limiting Toxicity (DLT) | 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. | Cycle 1: Days 1 to 28 |
| Objective Response Rate (ORR) | 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. | At screening and thereafter every 2 cycles of treatment until disease progression (Up to 65.8 weeks) |
| 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 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for MLN0128 | 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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Inclusion Criteria:
Exclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fort Myers | Florida | 33905 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28601972 | Derived | Burris HA 3rd, Kurkjian CD, Hart L, Pant S, Murphy PB, Jones SF, Neuwirth R, Patel CG, Zohren F, Infante JR. TAK-228 (formerly MLN0128), an investigational dual TORC1/2 inhibitor plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2017 Aug;80(2):261-273. doi: 10.1007/s00280-017-3343-4. Epub 2017 Jun 10. |
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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.
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Participants with advanced solid malignancies enrolled in the dose escalation phase to establish MTD: MLN0128 6,7,8,9,10 mg QDx3d QW, 7mg QDx5d QW or 30, 40 mg QW. The expansion phase enrolled participants in either A: HER2- cancer participants, MLN0128 at MTD+paclitaxel or B: HER2+ cancer participants, MLN0128 at MTD+paclitaxel+trastuzumab.
Participants took part in the study at three investigative sites in the United States from 28 February 2011 to 15 Sep 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | MLN0128P 30 or 40 mg QW | MLN0128 and paclitaxel (MLN0128P): MLN0128 30 or 40 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 until Maximum Tolerated Dose (MTD) was established (Up to 15.3 weeks). |
| FG001 |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 7, 2013 | Feb 13, 2019 |
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| MLN0128P 9 mg QD×3d QW | Experimental | 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. |
|
| MLN0128P 10 mg QD×3d QW | Experimental | 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. |
|
| MLN0128P 7 mg QD×5d QW | Experimental | 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. |
|
| MLN0128P 8 mg QD×3d QW HER2- | Experimental | 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. |
|
| MLN0128PH 8 mg QD×3d QW HER2+ | Experimental | 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. |
|
| paclitaxel | Drug | paclitaxel intravenous infusion |
|
| trastuzumab | Drug | trastuzumab intravenous infusion |
|
| First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks) |
| Cycles 1 and 2: Day 1 or 2 |
| Cmin: Minimum Observed Plasma Concentration for MLN0128 | 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. | Cycles 1 and 2: Day 1 or 2 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0128 | 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. | Cycles 1 and 2: Day 1 or 2 |
| Terminal Phase Elimination Half-life (T1/2) for MLN0128 | Cycle 1 Day 1 |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128 | Cycle 1 Day 1 |
| AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for MLN0128 | 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. | Cycles 1 and 2: Day 1 or 2 |
| Cmax: Maximum Observed Plasma Concentration for Paclitaxel | Cycles 1 and 2: Day 1 |
| Cmin: Minimum Observed Plasma Concentration for Paclitaxel | 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. | Cycles 1 and 2: Day 1 or 2 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Paclitaxel | Cycles 1 and 2: Day 1 |
| Terminal Phase Elimination Half-life (T1/2) for Paclitaxel | Cycle 1 Day 1 |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Paclitaxel | Cycle 1 Day 1 |
| AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for Paclitaxel | Cycle 1 Day 1 |
| AUC(0-24): Area Under the Plasma Concentration-time Curve Extrapolated to 24 Hours for Paclitaxel | Cycle 1 Day 1 |
| CL: Total Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel | Cycle 1 Day 1 |
| Vss: Volume of Distribution at Steady State Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel | Cycle 1 Day 1 |
| Oklahoma City |
| Oklahoma |
| 73104 |
| United States |
| Nashville | Tennessee | 37203 | United States |
| MLN0128P 6, 7, 8, 9 or 10 mg QD×3d QW |
MLN0128 and paclitaxel (MLN0128P): MLN0128 6 , 7, 8, 9 or 10 mg, capsule, orally, once daily (QD) 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 until MTD was established (Up to 87.4 weeks). |
| FG002 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
| FG003 | Expansion Cohort MLN0128P 8 mg QD×3d QW HER2- | MLN0128 and paclitaxel (MLN0128P): 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 (Up to 61.6 weeks). |
| FG004 | Expansion Cohort MLN0128PH 8mg QD×3d QW HER2+ Plus Trastuzumab | 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 (Up to 23.4 weeks). |
|
| Treated |
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| Dose-escalation Evaluable |
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| COMPLETED |
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| NOT COMPLETED |
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All Subjects as Treated (ASaT) population, which consisted of all enrolled participants who received at least 1 dose of MLN0128.
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| ID | Title | Description |
|---|---|---|
| BG000 | MLN0128P 30 or 40 mg QW | MLN0128 and paclitaxel (MLN0128P): MLN0128 30 or 40 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 until Maximum Tolerated Dose (MTD) was established (Up to 15.3 weeks). |
| BG001 | MLN0128P 6, 7, 8, 9 or 10 mg QD×3d QW | MLN0128 and paclitaxel (MLN0128P): MLN0128 6 , 7, 8, 9 or 10 mg, capsule, orally, once daily (QD) 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 until MTD was established (Up to 87.4 weeks). |
| BG002 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
| BG003 | Expansion Cohort MLN0128P 8 mg QD×3d QW HER2- | MLN0128 and paclitaxel (MLN0128P): 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 (Up to 61.6 weeks). |
| BG004 | Expansion Cohort MLN0128PH 8mg QDx3d QW HER2+ Plus Trastuzumab | 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 (Up to 23.4 weeks). |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
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| Primary | Dose Escalation Phase: Maximum Tolerated Dose (MTD) | MTD is the highest dose level at which the participants tolerate treatment without dose-limiting toxicities during the first cycle (28 days) of therapy. | Safety Population included all participants who received at least one dose of study drug. | Posted | Number | mg (QD×3d QW) | Cycle 1: Days 1 to 28 |
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| Primary | Dose Escalation Phase: Number of Participants With at Least 1 Dose Limiting Toxicity (DLT) | 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. | Dose-Escalation evaluable population included participants who received ≥ 75% of planned doses of MLN0128 in Cycle 1 or stopped study drug before receiving 75% of doses because of study drug-related AEs (considered as DLT). | Posted | Number | participants | Cycle 1: Days 1 to 28 |
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| Primary | Objective Response Rate (ORR) | 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. | Full Analysis Set (FAS) included all participants who received 1 or more doses of MLN0128 and have adequate baseline and post-baseline data collected. | Posted | Number | percentage of participants | At screening and thereafter every 2 cycles of treatment until disease progression (Up to 65.8 weeks) |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for MLN0128 | 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. | Pharmacokinetic (PK) population included all participants enrolled during Dose Escalation phase, received at least 1 dose of MLN0128 and had sufficient concentration-time data to calculate PK parameters, with data available for Cmax. Here, number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Mean | Full Range | ng/mL | Cycles 1 and 2: Day 1 or 2 |
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| Secondary | Cmin: Minimum Observed Plasma Concentration for MLN0128 | 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. | Due to the change in planned analysis, minimum plasma concentration data was not collected. | Posted | Cycles 1 and 2: Day 1 or 2 |
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| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0128 | 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. | PK population included all participants enrolled during Dose Escalation phase, received at least 1 dose of MLN0128 and had sufficient concentration-time data to calculate PK parameters, with data available for Tmax. Here, number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Median | Full Range | hours | Cycles 1 and 2: Day 1 or 2 |
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| Secondary | Terminal Phase Elimination Half-life (T1/2) for MLN0128 | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of MLN0128 and had sufficient concentration-time data to calculate 1 or more PK parameters. T1/2 data is only available for 2 participants in the MLN0128P 6 mg QD×3d QW and 2 participants in the MLN0128P 7 mg QD×3d QW arm. | Posted | Mean | Full Range | hours | Cycle 1 Day 1 |
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| Secondary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128 | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of MLN0128 and had sufficient concentration-time data to calculate 1 or more PK parameters. AUC∞ data is only available for 2 participants in each the MLN0128P 6 mg QD×3d QW and MLN0128P 7 mg QD×3d QW arms. | Posted | Mean | Full Range | ng*hr/mL | Cycle 1 Day 1 |
|
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| Secondary | AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for MLN0128 | 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. | PK population included all participants enrolled during Dose Escalation phase, received at least 1 dose of MLN0128 and had sufficient concentration-time data to calculate PK parameters. Here, number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Mean | Full Range | ng*hr/mL | Cycles 1 and 2: Day 1 or 2 |
| |||||||||||||||||||||||||||
| Secondary | Cmax: Maximum Observed Plasma Concentration for Paclitaxel | PK population included all participants enrolled during Dose Escalation phase, received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate PK parameters, with data available for Cmax. Here, number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Mean | Full Range | ng/mL | Cycles 1 and 2: Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | Cmin: Minimum Observed Plasma Concentration for Paclitaxel | 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. | Due to the change in planned analysis, minimum plasma concentration data was not collected. | Posted | Cycles 1 and 2: Day 1 or 2 |
| ||||||||||||||||||||||||||||||
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Paclitaxel | PK population consisted of all participants enrolled during Dose Escalation phase of study who received at least 1 dose of MLN0128 or paclitaxel and had sufficient concentration-time data to calculate PK parameters for either compound. Here, number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Median | Full Range | hours | Cycles 1 and 2: Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | Terminal Phase Elimination Half-life (T1/2) for Paclitaxel | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate 1 or more PK parameters. T1/2 data is only available for participants in the MLN0128P 6,7,9 and 10 mg QD×3d QW arms. | Posted | Mean | Full Range | hours | Cycle 1 Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Paclitaxel | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate 1 or more PK parameters. AUC∞ data is only available for participants in the MLN0128P 6,7,9 and 10 mg QD×3d QW arms. | Posted | Mean | Full Range | ng*hr/mL | Cycle 1 Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for Paclitaxel | Participants from the PK population, all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate 1 or more PK parameters, with data available for analyses. | Posted | Mean | Full Range | ng*hr/mL | Cycle 1 Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | AUC(0-24): Area Under the Plasma Concentration-time Curve Extrapolated to 24 Hours for Paclitaxel | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate 1 or more PK parameters. AUC0-24 data is only available for participants in the MLN0128P 6,7,9 and 10 mg QD×3d QW arms. | Posted | Mean | Full Range | ng*hr/mL | Cycle 1 Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | CL: Total Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate 1 or more PK parameters. CL data is only available for participants in the MLN0128P 6,7,9 and 10 mg QD×3d QW arms. | Posted | Mean | Full Range | L/hr | Cycle 1 Day 1 |
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| Secondary | Vss: Volume of Distribution at Steady State Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel | PK population consisted of all participants enrolled during the Dose Escalation phase of the study who received at least 1 dose of paclitaxel and had sufficient concentration-time data to calculate 1 or more PK parameters. Vss data is only available for participants in the MLN0128P 6,7,9 and 10 mg QD×3d QW arms. | Posted | Mean | Full Range | L | Cycle 1 Day 1 |
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| Primary | 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 | 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. | All Subjects as Treated (ASaT) population consisted of all enrolled participants who received at least 1 dose of MLN0128, was used in the safety analyses. | Posted | Number | percentage of participants | First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks) |
|
First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. According to the protocol analysis planned, data was collected as per the dosing schedule.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MLN0128P 30 or 40 mg QW | MLN0128 and paclitaxel (MLN0128P): MLN0128 30 or 40 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 until Maximum Tolerated Dose (MTD) was established (Up to 15.3 weeks). | 2 | 8 | 5 | 8 | 8 | 8 |
| EG001 | MLN0128P 6, 7, 8, 9 or 10 mg QD×3d QW | MLN0128 and paclitaxel (MLN0128P): MLN0128 6 , 7, 8, 9 or 10 mg, capsule, orally, once daily (QD) 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 until MTD was established (Up to 87.4 weeks). | 2 | 29 | 12 | 29 | 29 | 29 |
| EG002 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). | 2 | 10 | 6 | 10 | 10 | 10 |
| EG003 | Expansion Cohort MLN0128P 8 mg QD×3d QW HER2- | MLN0128 and paclitaxel (MLN0128P): 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 (Up to 61.6 weeks). | 2 | 13 | 4 | 13 | 13 | 13 |
| EG004 | Expansion Cohort MLN0128PH 8mg QD×3d QW HER2+ Plus Trastuzumab | 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 (Up to 23.4 weeks). | 1 | 7 | 3 | 7 | 7 | 7 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oesophageal ulcer | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Diverticular perforation | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Enterocutaneous fistula | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (17.0) | Systematic Assessment | One treatment-emergent death occurred during treatment with 8 mg QDx3d QW HER2- dose cohort and is not related. |
|
| Sepsis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Laryngeal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Systematic Assessment | One treatment-emergent death occurred during treatment with 40 mg MLN0128 QW dose cohort and is not related. |
|
| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Systematic Assessment | Two treatment-emergent death occurred during treatment with 40 mg QW and 9 mg MLN0128 QD×3d QW dose cohort and are not related. |
|
| Neoplasm Progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Systematic Assessment |
| |
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Systematic Assessment | One treatment-emergent death occurred during treatment with MLN0128 8 mg QD×3d QW HER2+ Plus Trastuzumab dose cohort and is not related. |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment | One treatment-emergent death occurred during treatment with 8 mg QDx3d QW HER2- dose cohort and is not related. |
|
| Fatigue | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Tracheal obstruction extrinsic | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment | One treatment-emergent death occurred during treatment with 7 mg MLN0128 QD×5d QW dose cohort and is not related |
|
| Myocardial infarction | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Female genital tract fistula | Reproductive system and breast disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Disease Progression | General disorders | MedDRA (17.0) | Systematic Assessment | Two treatment-emergent death occurred during treatment with 9 mg MLN0128 QD×3d QW and 7 mg QD×5d QW dose cohort and are not related. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hyperammonaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypophagia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hyperchlorhydria | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Lip swelling | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oesophageal obstruction | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dyspnoea paroxysmal nocturnal | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pharyngeal lesion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nail bed tenderness | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hirsutism | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Feeling jittery | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Puncture site haemorrhage | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hyperaesthesia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Restless legs syndrome | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Abscess neck | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Catheter site cellulitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Labyrinthitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Low density lipoprotein increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| White blood cells urine positive | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| High density lipoprotein decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Protein total decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood cholosterol increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood chloride decreased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood chloride increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Carbon dioxide increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Prothrombin time prolonged | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Fistula | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Urine odour abnormal | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Orbital Oedema | Eye disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Arhropod bite | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Claustrophobia | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Adjustment disorder with depressed mood | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypoacusis | Ear and labyrinth disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Inguinal Hernia | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Lower respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Paranasal Sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Visual field defect | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Superior vena cava occlusion | Vascular disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Burn oral cavity | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Gastrointestinal viral infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA (17.0) | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Cushingoid | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.0) | Systematic Assessment |
|
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda | +1-866-835-2233 | trialdisclosures@takeda.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Mar 5, 2014 | Feb 13, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C572449 | sapanisertib |
| D017239 | Paclitaxel |
| D000068878 | Trastuzumab |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Asian |
|
| Black or African American |
|
| White |
|
| OG002 | MLN0128P 6 mg QD×3d QW | MLN0128 6 mg, capsule, orally, once daily (QD) 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 until MTD was established. |
| OG003 | 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
|
|
| OG002 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
| OG003 | Expansion Cohort MLN0128P 8 mg QD×3d QW HER2- | MLN0128 and paclitaxel (MLN0128P): 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 (Up to 61.6 weeks). |
| OG004 | Expansion Cohort MLN0128PH 8mg QDx3d QW HER2+ Plus Trastuzumab | 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 (Up to 23.4 weeks). |
|
|
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 until MTD was established.
| OG002 | MLN0128P 6 mg QD×3d QW | MLN0128 6 mg, capsule, orally, once daily (QD) 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 until MTD was established. |
| OG003 | 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
|
|
| OG002 |
| MLN0128P 6 mg QD×3d QW |
MLN0128 6 mg, capsule, orally, once daily (QD) 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 until MTD was established. |
| OG003 | 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
|
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 until MTD was established.
| OG002 | MLN0128P 6 mg QD×3d QW | MLN0128 6 mg, capsule, orally, once daily (QD) 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 until MTD was established. |
| OG003 | 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
|
|
|
|
| OG002 | MLN0128P 6 mg QD×3d QW | MLN0128 6 mg, capsule, orally, once daily (QD) 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 until MTD was established. |
| OG003 | 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
|
|
| 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
|
|
| OG002 |
| MLN0128P 6 mg QD×3d QW |
MLN0128 6 mg, capsule, orally, once daily (QD) 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 until MTD was established. |
| OG003 | 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
|
| OG003 |
| 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
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| OG003 |
| 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 until MTD was established. |
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| OG003 | 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 until MTD was established. |
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| 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 until MTD was established. |
| OG004 | 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 until MTD was established. |
| OG005 | 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 until MTD was established. |
| OG006 | 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 until MTD was established. |
| OG007 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
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| OG003 | 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 until MTD was established. |
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| OG003 | 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 until MTD was established. |
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| OG003 | 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 until MTD was established. |
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| MLN0128P 6, 7, 8, 9 or 10 mg QD×3d QW |
MLN0128 and paclitaxel (MLN0128P): MLN0128 6 , 7, 8, 9 or 10 mg, capsule, orally, once daily (QD) 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 until MTD was established (Up to 87.4 weeks). |
| OG002 | MLN0128P 7 mg QD×5d QW | MLN0128 and paclitaxel (MLN0128P): 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 until MTD was established (Up 65.4 weeks). |
| OG003 | Expansion Cohort MLN0128P 8 mg QD×3d QW HER2- | MLN0128 and paclitaxel (MLN0128P): 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 (Up to 61.6 weeks). |
| OG004 | Expansion Cohort MLN0128PH 8mg QDx3d QW HER2+ Plus Trastuzumab | 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 (Up to 23.4 weeks). |
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