Phase 2 Study of Alisertib (MLN8237) in Combination With... | NCT02038647

ID	Type	Description
2013-003713-18	EudraCT Number
U1111-1154-9805	Registry Identifier	WHO
DRKS00007849	Registry Identifier	DRKS

Label	Type	Description	Intervention Names
Alisertib (MLN8237) + Paclitaxel	Experimental	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day until disease progression (Up to 17 Cycles).	Drug: Alisertib Drug: Paclitaxel
Placebo + Paclitaxel	Placebo Comparator	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).	Drug: Placebo Drug: Paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Alisertib	Drug	Alisertib tablets	Alisertib (MLN8237) + Paclitaxel	MLN8237

Measure	Description	Time Frame
Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines	PFS is defined as time in days from start of study treatment to first documentation of objective tumor progression based on Investigator's assessment or up to death due to any cause, whichever occurs first based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Progressive disease (PD) was defined as ≥20% increase in sum longest diameter (LD) in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)

Measure	Description	Time Frame
Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An Adverse Event (AE) is defined as any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with treatment. An AE can be any unfavorable and unintended sign (eg, clinically significant abnormal laboratory finding), symptom, or disease temporally associated with use of drug, whether or not it is considered related to drug. A treatment-emergent adverse event (TEAE) is defined as an AE with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) is any experience that suggests 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 congenital anomaly/birth defect or is medically significant per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Measure	Description	Time Frame
Biomarker Correlative Studies Including Circulating Tumor Cells and Circulating DNA Assessments		Day 1 cycle 1 in a 28-day cycle
Health Related Quality of Life (HRQOL )		Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Each participant must meet all the following inclusion criteria to be enrolled in the study:

Male or female participants ≥ 18 years old.
Have a pathologically (histology or cytology) confirmed diagnosis of SCLC.
Have received and progressed after a platinum-based standard chemotherapy regimen for first line treatment of SCLC, either limited stage (LS) or extensive stage (ES).
Have measurable disease within ≤ 2 weeks before randomization. Clear radiographic evidence of disease progression after initial therapy should have been documented.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0-1).
Participants with treated brain metastases (surgery, whole or stereotactic brain radiation) are allowed provided the lesions have been stable for at least 2 weeks and the participant is off steroids or is on a stable dose of steroids. Participants should be without neurologic dysfunction that would confound the evaluation of neurological and/or other AEs.

Exclusion Criteria

Participants meeting any of the following exclusion criteria are not to be randomized to treatment:

Any prior therapy for second-line treatment of SCLC.
Participants who relapsed ≥ 180 days after their response to first-line treatment.
Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib, or any other investigational agent.
Prior treatment with paclitaxel or any other taxane agent.
Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.
Any comorbid condition or unresolved toxicity that would preclude administration of alisertib or weekly paclitaxel.
Prior history of ≥ Grade 2 neurotoxicity that is not resolved to ≤ Grade 1.
Participants with symptomatic and/or progressive brain metastases or with carcinomatous meningitis.
Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of alisertib and during study conduct. Major prohibited enzyme inducers include: phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, and St. John's wort.
Inability to swallow alisertib or other orally administered medications.
Requirement for administration of proton pump inhibitor (PPI), H2 antagonist, or pancreatic enzymes.
Diagnosed with or treated for another malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease.
Other severe acute or chronic medical or psychiatric condition(s) per protocol.
History of myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac arrhythmias of Grade > 2, thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving the first dose of study drug.
Known history of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C.
Surgery within 3 weeks (or 2 weeks for a minor surgery) before study enrollment and not fully recovered to baseline or to a stable clinical status.
Participants who are pregnant, lactating, or do not agree to use effective methods of contraception during the study treatment period through 6 months after the last dose of study drug per protocol.

Name	Affiliation	Role
Medical Director Clinical Science	Millennium Pharmaceuticals, Inc.	Study Director

PubMed Identifier	Type	Citation	Retractions
31655296	Derived	Owonikoko TK, Niu H, Nackaerts K, Csoszi T, Ostoros G, Mark Z, Baik C, Joy AA, Chouaid C, Jaime JC, Kolek V, Majem M, Roubec J, Santos ES, Chiang AC, Speranza G, Belani CP, Chiappori A, Patel MR, Czebe K, Byers L, Bahamon B, Li C, Sheldon-Waniga E, Kong EF, Williams M, Badola S, Shin H, Bedford L, Ecsedy JA, Bryant M, Jones S, Simmons J, Leonard EJ, Ullmann CD, Spigel DR; C14018 study investigators. Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses. J Thorac Oncol. 2020 Feb;15(2):274-287. doi: 10.1016/j.jtho.2019.10.013. Epub 2019 Oct 23.

ID	Title	Description
FG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
FG001

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

Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines

PFS is defined as time in days from start of study treatment to first documentation of objective tumor progression based on Investigator's assessment or up to death due to any cause, whichever occurs first based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Progressive disease (PD) was defined as ≥20% increase in sum longest diameter (LD) in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The intent-to-treat (ITT) population was defined as all participants who were randomized to study treatment. For participants who have not progressed and is last known to be alive, PFS was censored at the last response assessment that is stable disease (SD) or better as determined by Investigator, and analyzed using FDA Guidelines.

Posted

Median

95% Confidence Interval

days

Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Units	Counts
Participants	OG00089 OG00189

Title

Denominators

Categories

Title	Measurements
	OG000101(80 to 113) OG00166(53 to 83)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.113	P-value tests the hypothesis of equal event times in both treatment arms obtained using the Log-rank test stratified by disease subtype as sensitive versus resistant/refractory and the presence of brain metastases.	Hazard Ratio (HR)	0.77			2-Sided	95	0.557	1.067			The stratification factors were: disease subtype as sensitive versus resistant/refractory and the presence of brain metastases (yes or no) with treatment (Alisertib + Paclitaxel vs Placebo + Paclitaxel) as a factor in the model.		Superiority

Secondary

Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An Adverse Event (AE) is defined as any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with treatment. An AE can be any unfavorable and unintended sign (eg, clinically significant abnormal laboratory finding), symptom, or disease temporally associated with use of drug, whether or not it is considered related to drug. A treatment-emergent adverse event (TEAE) is defined as an AE with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) is any experience that suggests 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 congenital anomaly/birth defect or is medically significant per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

The safety population was defined as all participants who received at least 1 dose of any study drug.

Posted

Number

percentage of participants

From the first dose through 30 days after the last dose of study medication: data cut-off 03 January 2016 (Up to 10.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).

Secondary

Overall Survival (OS)

OS was defined as the time in days from the date of randomization to the date of death due to any cause.

The ITT population was defined as all participants who were randomized to study treatment. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive.

Posted

Median

95% Confidence Interval

days

Contact every 2 months after EOT/disease progression until the sooner of death, study closure, or 14 months after the last participant was randomized up to data cut-off: 3 January 2016 (approximately 22 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Secondary

Overall Response Rate (ORR)

ORR is defined as the percentage of participants who achieved CR or partial response (PR) as best response based on Investigator's assessment according to RECIST v 1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as ≥ 30% decrease in sum of LD of target lesions in reference to Baseline sum LD.

The ITT population was defined as all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Secondary

Complete Response Rate (CRR)

CRR is defined as the percentage of participants who achieved CR as best response and based on Investigator's assessment according to RECIST v 1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.

The ITT population was defined as all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Secondary

Disease Control Rate (DCR)

DCR was defined as the percentage of participants who achieved CR, PR, or SD (when SD was a minimum of 8 weeks in duration). Duration of SD was defined as the time from the date of randomization to the date of first documentation of disease progression for participants who achieved SD as their best overall response. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as ≥ 30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The ITT population was defined as all participants who were randomized to study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel

Secondary

Duration of Response (DOR)

DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders. PR was defined as ≥ 30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The ITT population was defined as all participants who were randomized to study treatment. Responders were evaluated for this outcome measure. Responders without documentation of PD were censored at their date of last response assessment that was SD or better.

Posted

Median

95% Confidence Interval

days

From first documented response until disease progression until data cut-off 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Secondary

Change From Baseline in Symptom (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) Score at Cycle 5

European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is 30-item questionnaire with 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (fatigue, nausea, vomiting and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions use 7-point scale (1=very poor - 7=Excellent). Total Score=0-100 scale; for 5 functional scales and global quality-of-life scale, a higher score=a better level of functioning. For symptoms scale, higher score= higher level of symptoms. EORTC QLQ-LC13 is considered as standard instrument to assess the quality of life (QL) of lung cancer participants. Total Score=0-100. Higher score=increase in level of symptomatology. The change between (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) score collected at Cycle 5 relative to baseline.

The ITT population was defined as all participants who were randomized to study treatment. Here number of participants analyzed are participants evaluated in this outcome measure at the specific timepoint.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline up to Cycle 5 (approximately 4.6 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).

Secondary

Percentage of Participants Experiencing Symptom Relief

Percentage of participants experiencing symptom relief, including coughing relief, dyspnea relief, and pain relief. Coughing relief is defined as a decrease from baseline ≥ 10 in QLQ-LC13 cough scale/item score. Dyspnea relief is defined as a decrease from baseline ≥ 10 in QLQ-C30 dyspnea scale/item score. Pain relief is defined as a decrease from baseline ≥ 10 in QLQ-C30 pain scale score. EORTC QLQ-C30 is 30-item questionnaire with 5 functional scales, 1 global health status scale, 3 symptom scales, 6 single items. Total Score=0-100 scale; for 5 functional scales and global quality-of-life scale, a higher score=a better level of functioning. For symptoms scale, higher score= higher level of symptoms. EORTC QLQ-LC13 is considered as standard instrument to assess the QL of lung cancer participants. Total Score=0-100. Higher score=increase in level of symptomatology.

The ITT population was defined as all participants who were randomized to study treatment. Participants without coughing/dyspnea/pain relief were censored at their last assessment.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001

Secondary

Time to Symptom Relief

Time to symptom (coughing/dyspnea/pain) relief was defined as the time from the date of randomization to the date of first detection of coughing/dyspnea/pain relief, respectively.

The ITT population was defined as all participants who were randomized to study treatment. Participants without coughing/dyspnea/pain relief were censored at their last assessment.

Posted

Median

95% Confidence Interval

months

Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Units	Counts

Secondary

Time to Symptom Progression

Time to coughing/dyspnea/pain progression was defined as time from the date of randomization to date of first detection of progression. Coughing progression was defined as increase from baseline ≥10 in QLQ-LC13 cough scale/item score. Dyspnea progression was defined as increase from baseline ≥10 in QLQ-C30 dyspnea scale/item score. Pain progression was defined as increase from baseline ≥10 in QLQ-C30 pain scale score. EORTC QLQ-C30 is 30-item questionnaire with 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (fatigue, nausea, vomiting and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-LC13 is 13-item scale for assessing treatment-specific symptoms in lung cancer. Total Score= 0-100 scale; for 5 functional scales and global quality-of-life scale, higher score=better level of functioning. For symptoms scale, higher score=higher level of symptoms.

The ITT population was defined as all participants who were randomized to study treatment. Participant without coughing/dyspnea/pain progression were censored at their last assessment.

Posted

Median

95% Confidence Interval

months

Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).

Secondary

Observed Plasma Concentration for Alisertib

Safety population was defined as all participants who received at least 1 dose of any study drug. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours (hrs) post-dose

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).

Units	Counts
Participants	OG000

Secondary

Observed Plasma Concentration for Paclitaxel

Due to change in planned analysis, data was only collected and summarized for alisertib not for paclitaxel.

Posted

Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours post-dose

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).

Units	Counts
Participants	OG000

Other Pre-specified

Biomarker Correlative Studies Including Circulating Tumor Cells and Circulating DNA Assessments

This is an exploratory endpoint.

Posted

Day 1 cycle 1 in a 28-day cycle

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Units	Counts
Participants	OG000

Other Pre-specified

Health Related Quality of Life (HRQOL )

This is an exploratory endpoint.

Posted

Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)

ID	Title	Description
OG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
OG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is related with study drug.	EG00012 events9 affected87 at risk EG0010 events0 affected89 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment		EG0005 events5 affected87 at risk EG0010 events0 affected89 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.	EG0002 events2 affected87 at risk EG0011 events1 affected89 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0005 events5 affected87 at risk EG0010 events0 affected89 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0005 events4 affected87 at risk EG0011 events1 affected89 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0011 events1 affected89 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0012 events2 affected89 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Neutropenic sepsis	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is related with study drug.	EG0003 events2 affected87 at risk EG0010 events0 affected89 at risk
Bacteraemia	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Sepsis	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is related with study drug.	EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Septic shock	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is related with study drug.	EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Pneumonia	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.	EG0003 events3 affected87 at risk EG0013 events1 affected89 at risk
Pneumocystis jirovecii infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.	EG0000 events0 affected87 at risk EG0012 events1 affected89 at risk
Fungal infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Oral herpes	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Respiratory tract infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0011 events1 affected89 at risk
Influenza	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	Four treatment-emergent deaths occurred during treatment in Placebo + Paclitaxel arm group and are not related with study drug.	EG0000 events0 affected87 at risk EG0017 events6 affected89 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Metastases to peritoneum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	Two treatment-emergent deaths occurred during treatment in Alisertib+ Paclitaxel arm group and are not related with study drug.	EG0003 events2 affected87 at risk EG0010 events0 affected89 at risk
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	Two treatment-emergent death occurred during treatment in Alisertib+ Paclitaxel arm group and is not related with study drug.	EG0003 events3 affected87 at risk EG0010 events0 affected89 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.	EG0002 events1 affected87 at risk EG0011 events1 affected89 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.	EG0002 events2 affected87 at risk EG0011 events1 affected89 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is not related with study drug.	EG0002 events1 affected87 at risk EG0010 events0 affected89 at risk
Cardiac failure	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0011 events1 affected89 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Angina pectoris	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Pericardial effusion	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0012 events2 affected89 at risk
General physical health deterioration	General disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and two treatment-emergent deaths occurred during treatment in Alisertib + Paclitaxel arm group and are not related with study drug.	EG0004 events3 affected87 at risk EG0011 events1 affected89 at risk
Fatigue	General disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Pyrexia	General disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.	EG0001 events1 affected87 at risk EG0012 events2 affected89 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Epilepsy	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Seizure	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Ataxia	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Cognitive disorder	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0012 events2 affected89 at risk
Confusional state	Psychiatric disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Mental status changes	Psychiatric disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Aortic thrombosis	Vascular disorders	MedDRA Version 15.0	Systematic Assessment	One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is not related with study drug.	EG0002 events1 affected87 at risk EG0010 events0 affected89 at risk
Embolism	Vascular disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk
Paraplegia	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDRA Version 15.0	Systematic Assessment		EG0001 events1 affected87 at risk EG0010 events0 affected89 at risk
Erysipelas	Infections and infestations	MedDRA Version 15.0	Systematic Assessment		EG0000 events0 affected87 at risk EG0011 events1 affected89 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG000104 events48 affected87 at risk EG00132 events18 affected89 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00043 events30 affected87 at risk EG00138 events30 affected89 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00045 events28 affected87 at risk EG00127 events19 affected89 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00049 events27 affected87 at risk EG0017 events6 affected89 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00011 events8 affected87 at risk EG00125 events21 affected89 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00013 events12 affected87 at risk EG0014 events3 affected89 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0009 events7 affected87 at risk EG0016 events6 affected89 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0009 events8 affected87 at risk EG0014 events4 affected89 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0007 events5 affected87 at risk EG0015 events5 affected89 at risk
Dysphagia	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events5 affected87 at risk EG0013 events3 affected89 at risk
Fatigue	General disorders	MedDRA Version 15.0	Systematic Assessment	EG00052 events38 affected87 at risk EG00135 events28 affected89 at risk
Asthenia	General disorders	MedDRA Version 15.0	Systematic Assessment	EG00032 events14 affected87 at risk EG00116 events11 affected89 at risk
Oedema peripheral	General disorders	MedDRA Version 15.0	Systematic Assessment	EG0007 events6 affected87 at risk EG00114 events10 affected89 at risk
Pyrexia	General disorders	MedDRA Version 15.0	Systematic Assessment	EG0008 events8 affected87 at risk EG0017 events6 affected89 at risk
Non-cardiac chest pain	General disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events4 affected87 at risk EG0015 events5 affected89 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	EG00055 events38 affected87 at risk EG00123 events18 affected89 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	EG00089 events41 affected87 at risk EG00111 events7 affected89 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	EG00018 events12 affected87 at risk EG0018 events5 affected89 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	EG0007 events7 affected87 at risk EG0013 events3 affected89 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG00036 events29 affected87 at risk EG00126 events19 affected89 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG00012 events10 affected87 at risk EG0017 events6 affected89 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0008 events7 affected87 at risk EG0015 events4 affected89 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events5 affected87 at risk EG00110 events6 affected89 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0007 events7 affected87 at risk EG0011 events1 affected89 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0006 events5 affected87 at risk EG0011 events1 affected89 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00023 events21 affected87 at risk EG00122 events19 affected89 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00019 events17 affected87 at risk EG00118 events17 affected89 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0004 events4 affected87 at risk EG00112 events9 affected89 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0003 events3 affected87 at risk EG00110 events7 affected89 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events5 affected87 at risk EG0013 events3 affected89 at risk
Dizziness	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG00017 events15 affected87 at risk EG00114 events9 affected89 at risk
Headache	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0009 events9 affected87 at risk EG0017 events6 affected89 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG00010 events8 affected87 at risk EG00110 events7 affected89 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events4 affected87 at risk EG0019 events6 affected89 at risk
Hypoaesthesia	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events4 affected87 at risk EG0016 events5 affected89 at risk
Somnolence	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0006 events5 affected87 at risk EG0013 events3 affected89 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0002 events2 affected87 at risk EG0015 events5 affected89 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG00012 events9 affected87 at risk EG00110 events5 affected89 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0006 events6 affected87 at risk EG00111 events6 affected89 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0008 events5 affected87 at risk EG0019 events6 affected89 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0004 events4 affected87 at risk EG0015 events5 affected89 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0003 events3 affected87 at risk EG0017 events5 affected89 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected87 at risk EG0018 events6 affected89 at risk
Neutrophil count decreased	Investigations	MedDRA Version 15.0	Systematic Assessment	EG00028 events14 affected87 at risk EG0014 events4 affected89 at risk
Weight decreased	Investigations	MedDRA Version 15.0	Systematic Assessment	EG00018 events13 affected87 at risk EG0017 events5 affected89 at risk
White blood cell count decreased	Investigations	MedDRA Version 15.0	Systematic Assessment	EG00020 events12 affected87 at risk EG0014 events1 affected89 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG00015 events14 affected87 at risk EG0015 events5 affected89 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected87 at risk EG00110 events6 affected89 at risk
Insomnia	Psychiatric disorders	MedDRA Version 15.0	Systematic Assessment	EG0007 events7 affected87 at risk EG0018 events7 affected89 at risk
Confusional state	Psychiatric disorders	MedDRA Version 15.0	Systematic Assessment	EG0002 events2 affected87 at risk EG0015 events5 affected89 at risk
Hypertension	Vascular disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events5 affected87 at risk EG00113 events11 affected89 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment	EG0005 events5 affected87 at risk EG0014 events3 affected89 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0002 events2 affected87 at risk EG0015 events5 affected89 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Los Angeles	California		United States

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
BG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Alisertib + Paclitaxel	Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).	12	87	39	87	85	87
EG001	Placebo + Paclitaxel	Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).	11	89	30	89	80	89