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Trial record 9 of 59 for:    MLN8237

A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas

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ClinicalTrials.gov Identifier: NCT01512758
Recruitment Status : Completed
First Posted : January 19, 2012
Results First Posted : March 15, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Solid Tumors
Lymphomas
Intervention Drug: Alisertib
Enrollment 36
Recruitment Details Participants took part in the study at 8 investigative sites in Singapore, Taiwan, Hong Kong, and South Korea from 06 February 2012 to 08 October 2013.
Pre-assignment Details Participants with a diagnosis of advanced solid tumors or lymphomas received alisertib 30 mg or 40 mg twice a day (BID) for 7 consecutive days followed by a 14-day rest period in 21-day cycles (28-day cycles with additional 7-day rest period if all alisertib-related toxicities [except alopecia] were not resolved to less than Grade 2).
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2. Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Period Title: Overall Study
Started 30 6
Completed 30 [1] 6
Not Completed 0 0
[1]
Completed=Completed protocol-specified dosing and PK assessment.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg Total
Hide Arm/Group Description Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2. Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2. Total of all reporting groups
Overall Number of Baseline Participants 30 6 36
Hide Baseline Analysis Population Description
Safety Population is defined as all participants who received at least one dose of alisertib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 6 participants 36 participants
57.2  (9.52) 50.7  (18.25) 56.1  (11.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 6 participants 36 participants
Female
11
  36.7%
2
  33.3%
13
  36.1%
Male
19
  63.3%
4
  66.7%
23
  63.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 6 participants 36 participants
Asian (Chinese)
17
  56.7%
5
  83.3%
22
  61.1%
Asian (Korean)
13
  43.3%
0
   0.0%
13
  36.1%
Malay
0
   0.0%
1
  16.7%
1
   2.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Not Hispanic or Latino Number Analyzed 30 participants 6 participants 36 participants
30
 100.0%
6
 100.0%
36
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 6 participants 36 participants
Singapore
4
  13.3%
6
 100.0%
10
  27.8%
Taiwan
8
  26.7%
0
   0.0%
8
  22.2%
Hong Kong
5
  16.7%
0
   0.0%
5
  13.9%
Korea, Republic of
13
  43.3%
0
   0.0%
13
  36.1%
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 30 participants 6 participants 36 participants
162.5  (6.84) 161.9  (6.61) 162.4  (6.71)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 30 participants 6 participants 36 participants
57.78  (9.255) 62.30  (11.714) 58.53  (9.669)
Body Surface Area (BSA)   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 30 participants 6 participants 36 participants
1.611  (0.1487) 1.667  (0.1613) 1.620  (0.1499)
[1]
Measure Description: BSA = square root [height (cm) x weight (kg)/3600]
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
Hide Description MTD was defined as highest dose at which <2 participants experienced a dose-limiting toxicity (DLT). DLT was defined as any of the following events considered possibly related to therapy with alisertib by the investigator: 1. Grade 4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >7 days; 2. Grade 4 neutropenia with fever (oral or ear temperature ≥38.5°C); 3. Grade 4 thrombocytopenia (platelets <25,000/mm^3) for >7 days; 4. Platelet count <10,000 cells/mm^3; 5. ≥Grade 3 thrombocytopenia with clinically significant bleeding; 6. Delay in initiation of subsequent cycle by >7 days due to treatment-related toxicity; 7. ≥Grade 3 nonhematological toxicity except following: a. ≥Grade 3 nausea and/or emesis in the absence of optimal antiemetic therapy; b. ≥Grade 3 diarrhea in the absence of optimal supportive therapy; c. Grade 3 fatigue lasting <1 week; d. Other Grade 3 nonhematological toxicity that can be safely and reliably controlled to ≤Grade 2 with appropriate treatment.
Time Frame Treatment Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
DLT-Evaluable population is defined as participants with a common race who had not used granulocyte colony-stimulating factor (G-CSF) in cycle 1, and either experienced DLT during Cycle 1 or received at least 85% of planned doses of alisertib and have sufficient follow up data to allow investigator and sponsor to determine whether a DLT occurred.
Arm/Group Title Alisertib 30 mg or 40 mg
Hide Arm/Group Description:
Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities [except alopecia] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).
Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: mg
30
2.Primary Outcome
Title Number of Participants With Adverse Events and Serious Adverse Events
Hide Description 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 Serious Adverse Event (SAE) A serious 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.
Time Frame First dose to 30 days past last dose (Up to 12.1 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least one dose of alisertib.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Measure Type: Count of Participants
Unit of Measure: Participants
AE
30
 100.0%
6
 100.0%
SAE
15
  50.0%
4
  66.7%
3.Primary Outcome
Title Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events
Hide Description Laboratory AEs in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, investigations, and metabolism and nutrition disorders. An abnormal laboratory value was assessed as an AE if that value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment¬-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame First dose to 30 days past last dose (Up to 12.1 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least one dose of alisertib.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Measure Type: Count of Participants
Unit of Measure: Participants
Neutropenia
19
  63.3%
5
  83.3%
Anaemia
9
  30.0%
4
  66.7%
Thrombocytopenia
6
  20.0%
1
  16.7%
Febrile neutropenia
4
  13.3%
1
  16.7%
Leukopenia
2
   6.7%
2
  33.3%
White blood cell count decreased
7
  23.3%
0
   0.0%
Aspartate aminotransferase increased
6
  20.0%
0
   0.0%
Neutrophil count decreased
4
  13.3%
0
   0.0%
Alanine aminotransferase increased
4
  13.3%
0
   0.0%
Platelet count decreased
3
  10.0%
0
   0.0%
Blood bilirubin increased
2
   6.7%
0
   0.0%
Haemoglobin decreased
1
   3.3%
0
   0.0%
Blood creatinine increased
0
   0.0%
1
  16.7%
Urine output decreased
1
   3.3%
0
   0.0%
Hypokalaemia
4
  13.3%
3
  50.0%
Hypercalcaemia
0
   0.0%
1
  16.7%
Hyponatraemia
1
   3.3%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events
Hide Description Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
Time Frame First dose to 30 days past last dose (Up to 12.1 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least one dose of alisertib.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Measure Type: Count of Participants
Unit of Measure: Participants
Hypertension
1
   3.3%
0
   0.0%
Hypotension
1
   3.3%
0
   0.0%
Bradycardia
1
   3.3%
0
   0.0%
Pyrexia
8
  26.7%
1
  16.7%
5.Primary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Mean (Standard Deviation)
Unit of Measure: nM
Day 1 Number Analyzed 30 participants 6 participants
1442.5  (534.80) 1871.7  (429.62)
Day 7 Number Analyzed 28 participants 6 participants
3000.0  (1329.38) 3686.7  (885.45)
6.Primary Outcome
Title Tmax: Time to First Occurrence of Cmax for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Median (Full Range)
Unit of Measure: hr
Day 1 Number Analyzed 30 participants 6 participants
3.0
(2 to 8)
2.0
(2 to 3)
Day 7 Number Analyzed 28 participants 6 participants
2.9
(1 to 6)
2.0
(1 to 3)
7.Primary Outcome
Title AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval (τ) for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Mean (Standard Deviation)
Unit of Measure: nM*hr
Day 1 Number Analyzed 30 participants 6 participants
9549.0  (4119.30) 11811.7  (2845.76)
Day 7 Number Analyzed 28 participants 6 participants
24377.9  (13261.61) 30683.3  (9575.68)
8.Primary Outcome
Title Dose Normalized AUCτ: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib
Hide Description Dose normalized AUCτ was obtained using AUCτ divided by alisertib dose in milligrams.
Time Frame Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 28 6
Mean (Standard Deviation)
Unit of Measure: nM*hr/mg
812.9  (441.90) 766.8  (238.88)
9.Primary Outcome
Title T1/2: Terminal Half-Life for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 24 6
Mean (Standard Deviation)
Unit of Measure: hr
16.750  (8.1710) 14.795  (4.5715)
10.Primary Outcome
Title Rac: Accumulation Ratio for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 28 6
Mean (Standard Deviation)
Unit of Measure: ratio
2.830  (1.2955) 2.690  (1.0638)
11.Primary Outcome
Title PTR: Peak Trough Ratio During a Dosing Interval, at Steady State for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 28 6
Mean (Standard Deviation)
Unit of Measure: ratio
2.254  (0.6458) 2.207  (0.3946)
12.Primary Outcome
Title CLss/F: Apparent Clearance After Extravascular Administration, at Steady State, Calculated Using AUCτ for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 28 6
Mean (Standard Deviation)
Unit of Measure: L/hr
2.9357  (1.37091) 2.8083  (1.20259)
13.Secondary Outcome
Title Best Overall Response Rate Based on Investigator Assessment
Hide Description Best overall response rate is defined as the percentage of participants with complete response (CR) and/or partial response (PR) as assessed by the Investigator using Lymphoma International Working Group (IWG) Criteria or Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT, PET or MRI. IWG criteria for CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. RECIST response criteria is defined as: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions.
Time Frame Baseline and every 2 cycles for up to 24 months or until progressive disease
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least one dose of alisertib.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 30 6
Measure Type: Number
Unit of Measure: percentage of participants
CR 0 0
PR 3 0
14.Secondary Outcome
Title Duration of Response
Hide Description DOR is defined as the time from the date of first documentation of a CR response to the date of first documentation of PD according to IWG criteria or RECIST criteria 1.1. IWG PD is defined as PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. RECIST PD is defined as unequivocal progression of existing non-target lesions.
Time Frame First documented response until disease progression; approximately 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least one dose of alisertib. Participants with response were evaluated.
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 1 0
Median (Full Range)
Unit of Measure: days
169
(169 to 169)
15.Secondary Outcome
Title Concentrations of Relevant Tumor Markers
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1; at end of Cycle 2 and every 2 cycles thereafter; and at end treatment; approximately 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not analyzed as per the change in planned analysis (protocol amendment).
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description:
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame First dose to 30 days past last dose (Up to 12.1 Months)
Adverse Event Reporting Description 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.
 
Arm/Group Title Alisertib 30 mg Alisertib 40 mg
Hide Arm/Group Description Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2. Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
All-Cause Mortality
Alisertib 30 mg Alisertib 40 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alisertib 30 mg Alisertib 40 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   15/30 (50.00%)   4/6 (66.67%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  4/30 (13.33%)  1/6 (16.67%) 
Anaemia  1  1/30 (3.33%)  1/6 (16.67%) 
Leukopenia  1  1/30 (3.33%)  1/6 (16.67%) 
Neutropenia  1  2/30 (6.67%)  3/6 (50.00%) 
Gastrointestinal disorders     
Stomatitis  1  3/30 (10.00%)  1/6 (16.67%) 
Diarrhoea  1  2/30 (6.67%)  0/6 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/30 (3.33%)  0/6 (0.00%) 
Small intestinal obstruction  1  1/30 (3.33%)  0/6 (0.00%) 
Ascites  1  1/30 (3.33%)  0/6 (0.00%) 
Haematochezia  1  1/30 (3.33%)  0/6 (0.00%) 
General disorders     
Pyrexia  1  1/30 (3.33%)  0/6 (0.00%) 
Infections and infestations     
Bacteraemia  1  1/30 (3.33%)  0/6 (0.00%) 
Sepsis  1  1/30 (3.33%)  0/6 (0.00%) 
Subcutaneous abscess  1  0/30 (0.00%)  1/6 (16.67%) 
Urinary tract infection  1  1/30 (3.33%)  0/6 (0.00%) 
Investigations     
Platelet count decreased  1  1/30 (3.33%)  0/6 (0.00%) 
Neutrophil count decreased  1  1/30 (3.33%)  0/6 (0.00%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  0/30 (0.00%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  1/30 (3.33%)  0/6 (0.00%) 
Lower extremity mass  1  1/30 (3.33%)  0/6 (0.00%) 
Axillary mass  1  1/30 (3.33%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cholangiocarcinoma  1  1/30 (3.33%)  0/6 (0.00%) 
Cancer pain  1  0/30 (0.00%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  1/30 (3.33%)  0/6 (0.00%) 
Pulmonary embolism  1 [1]  1/30 (3.33%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
[1]
One treatment-emergent death occurred during treatment with alisertib 30 mg and was not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alisertib 30 mg Alisertib 40 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   30/30 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia  1  19/30 (63.33%)  3/6 (50.00%) 
Anaemia  1  8/30 (26.67%)  3/6 (50.00%) 
Thrombocytopenia  1  6/30 (20.00%)  1/6 (16.67%) 
Leukopenia  1  2/30 (6.67%)  2/6 (33.33%) 
Eye disorders     
Vision blurred  1  2/30 (6.67%)  0/6 (0.00%) 
Cataract  1  0/30 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders     
Diarrhoea  1  17/30 (56.67%)  3/6 (50.00%) 
Stomatitis  1  16/30 (53.33%)  2/6 (33.33%) 
Abdominal pain  1  6/30 (20.00%)  1/6 (16.67%) 
Abdominal pain upper  1  7/30 (23.33%)  0/6 (0.00%) 
Nausea  1  6/30 (20.00%)  1/6 (16.67%) 
Vomiting  1  5/30 (16.67%)  1/6 (16.67%) 
Oral pain  1  2/30 (6.67%)  2/6 (33.33%) 
Constipation  1  3/30 (10.00%)  0/6 (0.00%) 
Mouth ulceration  1  1/30 (3.33%)  2/6 (33.33%) 
Abdominal discomfort  1  2/30 (6.67%)  0/6 (0.00%) 
Haematochezia  1  2/30 (6.67%)  0/6 (0.00%) 
Anal ulcer  1  0/30 (0.00%)  1/6 (16.67%) 
Gingival pain  1  0/30 (0.00%)  1/6 (16.67%) 
General disorders     
Fatigue  1  12/30 (40.00%)  2/6 (33.33%) 
Pyrexia  1  7/30 (23.33%)  1/6 (16.67%) 
Asthenia  1  5/30 (16.67%)  0/6 (0.00%) 
Oedema peripheral  1  3/30 (10.00%)  0/6 (0.00%) 
Injection site pain  1  0/30 (0.00%)  1/6 (16.67%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  2/30 (6.67%)  1/6 (16.67%) 
Immune system disorders     
Contrast media allergy  1  2/30 (6.67%)  0/6 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  3/30 (10.00%)  0/6 (0.00%) 
Nasopharyngitis  1  2/30 (6.67%)  0/6 (0.00%) 
Injury, poisoning and procedural complications     
Skin wound  1  0/30 (0.00%)  1/6 (16.67%) 
Investigations     
White blood cell count decreased  1  7/30 (23.33%)  0/6 (0.00%) 
Aspartate aminotransferase increased  1  6/30 (20.00%)  0/6 (0.00%) 
Alanine aminotransferase increased  1  4/30 (13.33%)  0/6 (0.00%) 
Neutrophil count decreased  1  4/30 (13.33%)  0/6 (0.00%) 
Platelet count decreased  1  3/30 (10.00%)  0/6 (0.00%) 
Blood bilirubin increased  1  2/30 (6.67%)  0/6 (0.00%) 
Blood creatinine increased  1  0/30 (0.00%)  1/6 (16.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  8/30 (26.67%)  0/6 (0.00%) 
Hypokalaemia  1  4/30 (13.33%)  3/6 (50.00%) 
Hypercalcaemia  1  0/30 (0.00%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  3/30 (10.00%)  1/6 (16.67%) 
Pain in extremity  1  2/30 (6.67%)  0/6 (0.00%) 
Nervous system disorders     
Somnolence  1  4/30 (13.33%)  0/6 (0.00%) 
Lethargy  1  0/30 (0.00%)  3/6 (50.00%) 
Headache  1  2/30 (6.67%)  0/6 (0.00%) 
Psychiatric disorders     
Insomnia  1  4/30 (13.33%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  3/30 (10.00%)  0/6 (0.00%) 
Epistaxis  1  3/30 (10.00%)  0/6 (0.00%) 
Cough  1  1/30 (3.33%)  1/6 (16.67%) 
Productive cough  1  1/30 (3.33%)  1/6 (16.67%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  14/30 (46.67%)  3/6 (50.00%) 
Pruritus  1  7/30 (23.33%)  0/6 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  3/30 (10.00%)  3/6 (50.00%) 
Rash maculo-papular  1  3/30 (10.00%)  3/6 (50.00%) 
Skin hyperpigmentation  1  2/30 (6.67%)  2/6 (33.33%) 
Dry skin  1  1/30 (3.33%)  1/6 (16.67%) 
Pigmentation disorder  1  2/30 (6.67%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01512758     History of Changes
Other Study ID Numbers: C14013
1015004128 ( Registry Identifier: TCTIN )
U1111-1187-6744 ( Registry Identifier: WHO )
First Submitted: January 13, 2012
First Posted: January 19, 2012
Results First Submitted: April 9, 2018
Results First Posted: March 15, 2019
Last Update Posted: March 15, 2019