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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1164-7696 | Registry Identifier | WHO | |
| JapicCTI-152845 | Registry Identifier | JapicCTI |
Not provided
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Sponsor's decision
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The purpose of this study is to evaluate the safety and tolerability and determine the MTD to subsequently define an RP2D of alisertib in combination with weekly paclitaxel in East Asian participants with advanced solid tumors.
The drug being tested in this study was called alisertib. Alisertib in combination with paclitaxel was tested to find a safe and well-tolerated dose in East Asian participants. The study consisted of 2 parts: a dose escalation phase to determine the maximum tolerated dose (MTD) and define the recommended phase 2 dose (RP2D) of the alisertib plus paclitaxel combination in East Asian participants with advanced solid tumors; the second part is an expansion cohort at the RP2D of the alisertib plus paclitaxel in East Asian participants with either ovarian cancer or small cell lung cancer. This study looked at safety (lab results and side effects) and pharmacokinetic properties (how the drugs move throughout the body).
This open label study enrolled 9 participants. Dose Escalation Phase: Alisertib tablets at a starting dose of 15 mg, orally, twice daily, 3 days on/4 days off for 3 weeks in 28 day cycle in combination with paclitaxel, 60 mg/m^2 intravenous on days 1, 8, and 15 in 28-day cycles in Cohort 1 escalated to a dose of 25 mg alisertib, orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in Cohort 2. If ≥ 2 participants experience a dose limiting toxicity (DLT) the dose of alisertib decreased to 20 mg. Expansion Cohort: alisertib tablets at the determined RP2D dose orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in combination with paclitaxel, 60 mg/m^2 intravenous. Treatment was continued until disease progression or unacceptable toxicity.
This multi-centre trial was conducted in Japan and Korea. The overall time to participate in this study was up to 24 months.
The study was terminated early because of the sponsor's decision. Enrollment was completed in the dose escalation cohort, but no participants were enrolled in the dose expansion cohort.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Dose Escalation Phase) | Experimental | Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). |
|
| Cohort 2 (Dose Escalation Phase) | Experimental | Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT). |
|
| Dose Expansion Cohort | Experimental | Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alisertib | Drug | Alisertib tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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. | From Day 1 to 30 days after the last dose of study drug (approximately 21 months) |
| Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings | The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events. | From Day 1 to 30 days after the last dose of study drug (approximately 21 months) |
| Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings | The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events. | From Day 1 to 30 days after the last dose of study drug (approximately 21 months) |
| Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose | |
| Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Expansion Phase: Overall Response Rate (ORR) | ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) according to disease response based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months) |
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Inclusion Criteria:
Male or female participants 18 years or older (or minimum age of legal consent consistent with local regulations) at the time written study informed consent is obtained.
Participants of East Asian ethnicity (eg, Chinese, Japanese, or Korean).
Must have a diagnosis of a solid tumor malignancy (escalation part) or relapsed or refractory ovarian cancer (OC) or small cell lung cancer (SCLC) (expansion part).
No antineoplastic therapy (eg, drugs, biologicals, monoclonal antibodies, etc) or radiotherapy within the 3 weeks before enrollment (14 days for regimens with recovery expected within 7 to 14 days). The participant must have recovered (ie, ≤ Grade 1 toxicity or participant's baseline status, except alopecia) from all treatment-related toxicities.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate bone marrow function as defined by:
Adequate liver function as defined by:
Adequate renal function as defined by:
No more than 2 previous chemotherapy regimen in the metastatic setting.
Female participants who:
Male participants, even if surgically sterilized (ie, status postvasectomy), who:
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Suitable venous access for the study-required blood sampling, including pharmacokinetics (PK).
Ability to swallow tablets.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chiba | Japan | |||||
Participants with a diagnosis of Advanced Solid Tumors were enrolled in a dose escalation phase to receive a starting dose of alisertib 15 mg plus paclitaxel 60 mg/m^2. The dose expansion phase was not conducted.
Participants took part in the study at 3 investigative sites in Japan and Republic of Korea from 19 March 2015 to 23 May 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 (Dose Escalation Phase) | Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). |
| FG001 | Cohort 2 (Dose Escalation Phase) | Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT). |
| FG002 | Dose Expansion Cohort | Alisertib, MTD/RP2D determined in Dose Escalation Phase, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, IV on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population is defined as all participants who received at least 1 dose of alisertib. Participants were only enrolled in Dose Escalation Cohort 1.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 (Dose Escalation Phase) | Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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. | Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2. | Posted | Count of Participants | Participants | From Day 1 to 30 days after the last dose of study drug (approximately 21 months) |
|
First dose of study drug through 30 days after the last dose of any study drug (approximately 21 months)
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. Participants were only enrolled in Dose Escalation Cohort 1.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 (Dose Escalation Phase) | Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 25, 2017 | Apr 30, 2018 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jun 1, 2015 | Apr 30, 2018 | Prot_001.pdf |
Not provided
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D055752 | Small Cell Lung Carcinoma |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
Not provided
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| ID | Term |
|---|---|
| C550258 | MLN 8237 |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
Not provided
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| Paclitaxel | Drug | Paclitaxel intravenous solution |
|
| Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
| Dose Escalation Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
| Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel | Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Escalation Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Escalation Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Tme 0 to Infinity | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Escalation Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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. | From Day 1 to 30 days after the last dose of study drug |
| Dose Expansion Phase: Number of Participants With Clinically Significant Laboratory Findings | The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study. | From Day 1 to 30 days after the last dose of study drug |
| Dose Expansion Phase: Number of Participants With Clinically Significant Vital Sign Findings | The number of participants with any markedly abnormal vital sign values will be collected throughout study. | From Day 1 to 30 days after the last dose of study drug |
| Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Dose Expansion Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
| Shizuoka |
| Japan |
| Seoul | South Korea |
| Adverse Event |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Surface Area | Mean | Standard Deviation | m^2 |
|
| Cohort 1 (Dose Escalation Phase) |
Alisertib 15 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in a 28-day cycle until disease progression or unacceptable toxicity (Up to 22 Cycles). |
| OG001 | Cohort 2 (Dose Escalation Phase) | Alisertib 25 mg, tablet, orally, twice daily, (3 days on/4 days off for 3 weeks) on Days 1 to 3, 8 to 10 and 15 to 17 in 28 day cycles in combination with Paclitaxel 60 mg/m^2, intravenous (IV), on Days 1, 8, and 15 in 28-day cycle until disease progression or unacceptable toxicity. Dose of alisertib will be de-escalated to 20 mg if ≥ 2 participants experience a dose limiting toxicity (DLT). |
|
|
| Primary | Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings | The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events. | Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2. | Posted | Count of Participants | Participants | From Day 1 to 30 days after the last dose of study drug (approximately 21 months) |
|
|
|
| Primary | Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings | The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events. | Safety population is defined as all participants who received at least 1 dose of alisertib. No participants were enrolled in Dose Escalation Phase Cohort 2. | Posted | Count of Participants | Participants | From Day 1 to 30 days after the last dose of study drug (approximately 21 months) |
|
|
|
| Primary | Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Tme 0 to Infinity | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Escalation Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel | Pharmacokinetic data was not available as 9 participants were insufficient sample size to run the analysis. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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. | The dose expansion phase was cancelled by the sponsor. | Posted | From Day 1 to 30 days after the last dose of study drug |
|
|
| Primary | Dose Expansion Phase: Number of Participants With Clinically Significant Laboratory Findings | The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study. | The dose expansion phase was cancelled by the sponsor. | Posted | From Day 1 to 30 days after the last dose of study drug |
|
|
| Primary | Dose Expansion Phase: Number of Participants With Clinically Significant Vital Sign Findings | The number of participants with any markedly abnormal vital sign values will be collected throughout study. | The dose expansion phase was cancelled by the sponsor. | Posted | From Day 1 to 30 days after the last dose of study drug |
|
|
| Primary | Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Paclitaxel | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Primary | Dose Expansion Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel | The dose expansion phase was cancelled by the sponsor. | Posted | Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose |
|
|
| Secondary | Dose Expansion Phase: Overall Response Rate (ORR) | ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) according to disease response based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | The dose expansion phase was cancelled by the sponsor. | Posted | Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months) |
|
|
| 1 |
| 9 |
| 4 |
| 9 |
| 9 |
| 9 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
|
| Small cell lung cancer (disease progression) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Dizziness | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Intestinal perforation | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
|
| Blood antidiuretic hormone abnormal | Investigations | MedDRA version: 19.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Superior vena cava syndrome | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| Title | Measurements |
|---|---|
|