Study of MLN8237 in Participants With Advanced Hematological Malignancies
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00697346
Collaborator
(none)
58
10
3
99.3
5.8
0.1
Study Details
Study Description
Brief Summary
This is an open-label, multicenter, phase 1 study of MLN8237 in participants with advanced hematological malignancies for whom there are limited standard treatment options.
Detailed Description
The drug being tested in this study is called alisertib. Alisertib is being tested to treat people who have advanced hematological malignancies. This study determined the dose-limiting toxicity, maximum tolerated dose, safety and pharmacokinetics (how the drug moves through the body) for alisertib when given once or twice a day for 7 to 21 days.
This open label study enrolled 58 patients. Participants were enrolled in one of 3 treatment groups:
-
Part 1: Powder-in-Capsule (PIC) Dose Escalation (alisertib 25 mg PIC, orally twice daily [BID] on Day 1 [loading dose] and then alisertib 25 or 35 mg PIC once daily [QD] for 21 days (D), or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14D) in 28-day cycles
-
Part 1: Enteric-coated Tablet (ECT) Dose Escalation (alisertib 40 mg, ECT, orally, QD for 14D or alisertib 30, 40 or 50 mg, orally, BID for 7D) in 28-day cycles
-
Part 2: Participants with Peripheral T-cell Lymphoma (PTCL) (alisertib 50 mg ECT, orally, BID for 7D) in 21-day cycles
All participants received treatment for 12 months or until their disease progressed or they experienced unacceptable alisertib-related toxicity. This multi-center trial was conducted in the United States. The overall time to participate in this study was 422 days. Participants made multiple visits to the clinic, including a final visit 30 days after receiving their last dose of alisertib for a follow-up assessment.
Study Design
Study Type:
Interventional
Actual Enrollment
:
58 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
An Open-label, Phase 1 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients With Advanced Hematological Malignancies
Actual Study Start Date
:
Jul 11, 2008
Actual Primary Completion Date
:
Oct 1, 2016
Actual Study Completion Date
:
Oct 19, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: PIC Dose Escalation Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, (QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment. |
Drug: Alisertib
Alisertib (MLN8237) PIC or ECT
Other Names:
|
| Experimental: Part 1: ECT Dose Escalation Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles). |
Drug: Alisertib
Alisertib (MLN8237) PIC or ECT
Other Names:
|
| Experimental: Part 2: PTCL Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). |
Drug: Alisertib
Alisertib (MLN8237) PIC or ECT
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-Limiting Toxicity (DLT) [From first dose of study drug to 30 days after the last dose (up to 422 days)]
DLT was evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and was defined as any of the following events related to therapy with alisertib:1. Grade 4 neutropenia lasting ≥7 consecutive days, 2. Grade 4 neutropenia with fever and/or infection 3. Platelet count <25,000/mm^3 4. Grade 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis 5. Grade 3 or greater diarrhea despite maximal supportive therapy with loperamide 6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (<1 week) Grade 3 fatigue 7. Treatment delay of >21 days due to failure of adequate hematologic or non-hematologic recovery from previous cycle of treatment 8. Other alisertib related non-hematologic toxicities ≥Grade 2 that, in the opinion of the investigator required a dose reduction or discontinuation of therapy with alisertib.
- Maximum Tolerated Dose (MTD) of Alisertib [From first dose of study drug to 30 days after the last dose (up to 422 days)]
MTD was defined as the highest dose at which DLT occurred in 0/3 or 1/6 participants.
- Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose]
- AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose]
- Terminal Half-Life (t1/2) for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose]
- Accumulation Ratio (Rac) for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose]
- Peak/Trough Ratio for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose]
- CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 [Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Accumulation Ratio (Rac) for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Peak/Trough Ratio for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Terminal Half Life for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Peak/Trough Ratio for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 [Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 12 hours) postdose]
- Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1 [Cycle 1 Day 1 predose and at multiple timepoints (up to 12 hours) postdose]
- Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
- AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1 [Cycle 1 Days 1 predose and at multiple timepoints (up to 12 hours) postdose]
- AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
- Terminal Half-Life (t1/2) for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
- Accumulation Ratio (Rac) for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
- Peak/Trough Ratio for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
- CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 [Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose]
Secondary Outcome Measures
- Best Overall Response Rate Based on Investigator's Assessment [Baseline and every 2 cycles up to Month 12 until disease progression, 30 days after end of treatment (up to 422 days)]
Best overall response rate is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the Investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and the definition for PR includes at least a 50% decrease in sum of the product of the diameters and no new lesions.
- Duration of Response (DOR) [Baseline and every 2 cycles up to Month 12 until disease progression, 30 days after end of treatment (up to 422 days)]
DOR is defined as the time from the date of first documentation of a response (either CR or PR) to the date of first documentation of progressive disease (PD) according to International Working Group (IWG) criteria. CR is defined as the disappearance of all evidence of disease and the definition for PR includes at least a 50% decrease in sum of the product of the diameters and no new lesions. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
- Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 [Cycle 1 Day 1 predose]
One peripheral blood sample (approximately 4 mL) was to be obtained on Day 1 of Cycle 1 prior to the first dose of alisertib to genotype participants for polymorphisms in UGT1A1 because UGT1A1 is one of the enzymes responsible for glucuronidation of alisertib, which is expected to contribute to the clearance of alisertib. wt=wild type. *28=polymorphism in the promoter region of a UGT1A1 allele resulting in reduced UGT1A1 expression. Not determined = blood sample was not evaluable.
- Number of Participants With Polymorphisms in Aurora A Kinase [Cycle 1 Day 1 predose]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Relapsed or refractory disease and a histologically or cytologically confirmed hematological malignancy of the following type for which standard curative treatment does not exist or is no longer effective:
-
B-cell Follicular lymphoma
-
B-cell Marginal zone lymphoma
-
Diffuse large B-cell lymphoma
-
B-cell Mantle cell lymphoma
-
B-cell Small lymphocytic lymphoma (SLL)
-
B-Cell Chronic lymphocytic leukemia (B-CLL)
-
Multiple myeloma
-
Waldenstrom's macroglobulinemia
-
Noncutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
-
Angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma, enteropathy associated T-cell lymphoma (EATCL), NK lymphoma (NKL)
-
Participants with diffuse large B-cell lymphoma must have failed, be ineligible for, or have refused an autologous stem cell transplant. There is no restriction regarding the maximum number of prior regimens.
-
Aged 18 years or older
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
-
Radiographically or clinically evaluable disease for Part 1 of this study and measurable disease for Part 2 of this study
-
Suitable venous access for the conduct of blood sampling for MLN8237 pharmacokinetics (PK)
-
Recovered from the reversible effects of prior antineoplastic treatment (with the exception of alopecia and Grade 1 neuropathy)
Exclusion Criteria:
-
Pregnant or lactating
-
Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 as specified in the protocol
-
Prior allogeneic bone marrow (or other organ) transplantation
-
Newly diagnosed or uncontrolled cancer-related central nervous system (CNS) disease
-
Systemic antineoplastic treatment within 21 days preceding the first dose of study treatment. Exceptions requiring a 42-day recovery period from last treatment include: Nitrosoureas, mitomycin C or Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody (21 days if clear evidence of progressive disease)
-
Treatment with radioimmunoconjugates or toxin immunoconjugates such as ibritumomab tiuxetan (Zevalin™), or tositumomab (Bexxar®) within 56 days preceding the first dose of study treatment
-
Antineoplastic treatment with glucocorticoids within 21 days preceding the first dose of study treatment
-
Radiotherapy involving <25% of the hematopoietically active bone marrow within 21 days preceding first dose of study treatment
-
Radiotherapy involving ≥25% of the hematopoietically active bone marrow within 42 days preceding first dose of study treatment
-
Inability to swallow capsules or known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of MLN8237. Examples include, but are not limited to, partial gastrectomy, history of small intestine surgery, and celiac disease.
-
History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease
-
Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection. Testing is not required in the absence of clinical findings or suspicion.
-
Participants who fail to meet laboratory values as specified in the protocol during the screening period
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Scottsdale | Arizona | United States | ||
| 2 | Lexington | Kentucky | United States | ||
| 3 | Baltimore | Maryland | United States | ||
| 4 | Omaha | Nebraska | United States | ||
| 5 | Hackensack | New Jersey | United States | ||
| 6 | Buffalo | New York | United States | ||
| 7 | Chapel Hill | North Carolina | United States | ||
| 8 | Nashville | Tennessee | United States | ||
| 9 | Houston | Texas | United States | ||
| 10 | San Antonio | Texas | United States |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Director Clinical Science, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00697346
Other Study ID Numbers:
- C14003
- U1111-1187-1184
First Posted:
Jun 13, 2008
Last Update Posted:
May 31, 2019
Last Verified:
Feb 1, 2019
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 10 investigative sites in the United States from 11 July 2008 to19 October 2016. |
|---|---|
| Pre-assignment Detail | Participants with a diagnosis of advanced hematological malignancies were enrolled 1 of 3 treatment groups, Part 1:alisertib powder-in capsule (PIC) 25 to 90 mg dose escalation cohort, Part 1: alisertib 30 to 50 mg enteric-coated tablet (ECT) dose escalation cohort, or Part 2: alisertib ECT 50 mg participants with peripheral T-cell lymphoma (PTCL). |
| Arm/Group Title | Part 1: PIC Dose Escalation | Part 1: ECT Dose Escalation | Part 2: PTCL |
|---|---|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment. | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles). | Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). |
| Period Title: Overall Study | |||
| STARTED | 28 | 28 | 2 |
| COMPLETED | 0 | 2 | 1 |
| NOT COMPLETED | 28 | 26 | 1 |
Baseline Characteristics
| Arm/Group Title | Part 1: PIC Dose Escalation | Part 1: ECT Dose Escalation | Part 2: PTCL | Total |
|---|---|---|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment. | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles). | Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). | Total of all reporting groups |
| Overall Participants | 28 | 28 | 2 | 58 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
61.4
(8.91)
|
59.5
(14.22)
|
63.0
(24.04)
|
60.5
(12.03)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
14
50%
|
15
53.6%
|
2
100%
|
31
53.4%
|
| Male |
14
50%
|
13
46.4%
|
0
0%
|
27
46.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
9
32.1%
|
7
25%
|
0
0%
|
16
27.6%
|
| Not Hispanic or Latino |
19
67.9%
|
20
71.4%
|
2
100%
|
41
70.7%
|
| Unknown or Not Reported |
0
0%
|
1
3.6%
|
0
0%
|
1
1.7%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| White |
24
85.7%
|
26
92.9%
|
2
100%
|
52
89.7%
|
| Black or African American |
3
10.7%
|
1
3.6%
|
0
0%
|
4
6.9%
|
| Asian |
0
0%
|
1
3.6%
|
0
0%
|
1
1.7%
|
| Not Reported |
1
3.6%
|
0
0%
|
0
0%
|
1
1.7%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
28
100%
|
28
100%
|
2
100%
|
58
100%
|
| Height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
165.9
(11.25)
|
164.6
(10.95)
|
160.6
(6.43)
|
165.1
(10.89)
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
81.40
(20.031)
|
77.62
(19.747)
|
97.65
(43.911)
|
80.13
(20.573)
|
| Body Surface Area (m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [m^2] |
1.93
(0.282)
|
1.88
(0.289)
|
2.05
(0.434)
|
1.91
(0.286)
|
Outcome Measures
| Title | Number of Participants With Dose-Limiting Toxicity (DLT) |
|---|---|
| Description | DLT was evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and was defined as any of the following events related to therapy with alisertib:1. Grade 4 neutropenia lasting ≥7 consecutive days, 2. Grade 4 neutropenia with fever and/or infection 3. Platelet count <25,000/mm^3 4. Grade 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis 5. Grade 3 or greater diarrhea despite maximal supportive therapy with loperamide 6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (<1 week) Grade 3 fatigue 7. Treatment delay of >21 days due to failure of adequate hematologic or non-hematologic recovery from previous cycle of treatment 8. Other alisertib related non-hematologic toxicities ≥Grade 2 that, in the opinion of the investigator required a dose reduction or discontinuation of therapy with alisertib. |
| Time Frame | From first dose of study drug to 30 days after the last dose (up to 422 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT evaluable population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow up data to allow the investigators and sponsor to determine whether DLT occurred. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D | Alisertib 90 mg PIC QD 14D | Alisertib 40 mg ECT QD 14D | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 4 | 3 | 6 | 6 | 2 | 4 | 3 | 7 | 9 |
| Number [participants] |
1
3.6%
|
2
7.1%
|
0
0%
|
1
1.7%
|
2
NaN
|
2
NaN
|
2
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Title | Maximum Tolerated Dose (MTD) of Alisertib |
|---|---|
| Description | MTD was defined as the highest dose at which DLT occurred in 0/3 or 1/6 participants. |
| Time Frame | From first dose of study drug to 30 days after the last dose (up to 422 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT evaluable population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow up data to allow the investigators and sponsor to determine whether DLT occurred. |
| Arm/Group Title | Alisertib |
|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, PIC formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles) followed by alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles or alisertib 40 mg, ECT formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 58 |
| Number [mg BID for 7 days] |
50
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
833.2
(49.5)
|
1078.3
(26.4)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 3 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
1337.6
(57.8)
|
1451.9
(26.2)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 4 |
| Median (Full Range) [hours (h)] |
2.0
|
2.0
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 3 |
| Median (Full Range) [h] |
2.0
|
2.0
|
| Title | AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 3 |
| Geometric Mean (Geometric Coefficient of Variation) [nM*h] |
14846
(69.7)
|
16528
(35.6)
|
| Title | Terminal Half-Life (t1/2) for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 5 | 3 |
| Mean (Standard Deviation) [h] |
20.5
(7.3)
|
19.5
(6.0)
|
| Title | Accumulation Ratio (Rac) for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 3 |
| Mean (Standard Deviation) [ratio] |
1.9
(1.1)
|
1.5
(0.5)
|
| Title | Peak/Trough Ratio for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis, with data available at the given time point. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 3 |
| Mean (Standard Deviation) [ratio] |
6.0
(4.4)
|
4.3
(1.5)
|
| Title | CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis, with data available at the given time point. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 25mg PIC QD 21D | Alisertib 35 mg PIC QD 21D |
|---|---|---|
| Arm/Group Description | Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 | 3 |
| Geometric Mean (Geometric Coefficient of Variation) [L/h] |
3.2
(113)
|
4.1
(45)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D | Alisertib 90 mg PIC QD 14D |
|---|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 6 | 7 | 2 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
726.5
(34.8)
|
1637.0
(58.0)
|
1773.4
(44.3)
|
2497.4
(24.3)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D |
|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 | 5 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
2193.5
(NA)
|
1634.4
(52.5)
|
2300.2
(40.3)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D | Alisertib 90 mg PIC QD 14D |
|---|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 6 | 7 | 2 |
| Median (Full Range) [h] |
2.0
(34.8)
|
3.0
(58.0)
|
2.0
(44.3)
|
2.9
(24.3)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D |
|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 | 5 | 6 |
| Median (Full Range) [h] |
3.4
(NA)
|
2.0
(52.5)
|
2.0
(40.3)
|
| Title | AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D |
|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 | 5 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nM*h] |
23444
(NA)
|
19671
(64.8)
|
28864
(39.9)
|
| Title | Accumulation Ratio (Rac) for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D |
|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 | 5 | 6 |
| Mean (Standard Deviation) [ratio] |
2.4
(0.00)
|
1.5
(0.5)
|
1.9
(1.6)
|
| Title | Peak/Trough Ratio for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D |
|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 | 5 | 6 |
| Mean (Standard Deviation) [ratio] |
4.1
(NA)
|
5.4
(1.9)
|
4.4
(0.8)
|
| Title | CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 35 mg PIC QD 14D | Alisertib 45 mg PIC QD 14D | Alisertib 65 mg PIC QD 14D |
|---|---|---|---|
| Arm/Group Description | Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 | 5 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [L/h] |
2.9
(NA)
|
4.3
(44)
|
4.3
(53)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
1227
(41.3)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
1608
(NA)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 6 |
| Median (Full Range) [h] |
3.9
(NA)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 2 |
| Median (Full Range) [h] |
5.0
(NA)
|
| Title | AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [nM*h] |
14306
(20.3)
|
| Title | Terminal Half Life for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 1 |
| Mean (Standard Deviation) [h] |
11.7
(NA)
|
| Title | Peak/Trough Ratio for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 1 |
| Mean (Standard Deviation) [ratio] |
2.1
(NA)
|
| Title | CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 40 mg ECT QD 14D |
|---|---|
| Arm/Group Description | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 1 |
| Mean (Standard Deviation) [L/h] |
2.5
(NA)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 9 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
886
(39.7)
|
1114
(37.1)
|
1531
(58.4)
|
| Title | Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 8 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nM] |
2025
(29.6)
|
2586
(35.7)
|
2058
(44.6)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 9 | 10 |
| Median (Full Range) [h] |
2.0
(39.7)
|
2.2
(37.1)
|
2.0
(58.4)
|
| Title | Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 8 | 7 |
| Median (Full Range) [h] |
2.0
(39.7)
|
2.2
(37.1)
|
2.0
(58.4)
|
| Title | AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Days 1 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 9 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [nM*hr] |
5518
(18.3)
|
7095
(42.5)
|
9732
(48.5)
|
| Title | AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 8 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nM*hr] |
16024
(20.3)
|
18624
(27.3)
|
17914
(48.6)
|
| Title | Terminal Half-Life (t1/2) for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 1 | 4 | 5 |
| Mean (Standard Deviation) [h] |
13.3
(NA)
|
19.9
(10.7)
|
18.4
(13.9)
|
| Title | Accumulation Ratio (Rac) for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 7 | 6 |
| Mean (Standard Deviation) [ratio] |
2.9
(0.5)
|
2.8
(1.0)
|
2.3
(0.9)
|
| Title | Peak/Trough Ratio for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 7 | 7 |
| Mean (Standard Deviation) [ratio] |
2.5
(0.6)
|
2.4
(0.5)
|
2.5
(2.2)
|
| Title | CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7 |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure. |
| Arm/Group Title | Alisertib 30 mg ECT BID 7D | Alisertib 40 mg ECT BID 7D | Alisertib 50 mg ECT BID 7D |
|---|---|---|---|
| Arm/Group Description | Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). | Alisertib 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 3 | 7 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [L/h] |
3.7
(0.7)
|
4.4
(1.9)
|
6.7
(5.6)
|
| Title | Best Overall Response Rate Based on Investigator's Assessment |
|---|---|
| Description | Best overall response rate is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the Investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and the definition for PR includes at least a 50% decrease in sum of the product of the diameters and no new lesions. |
| Time Frame | Baseline and every 2 cycles up to Month 12 until disease progression, 30 days after end of treatment (up to 422 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The response-evaluable population is defined as all participants who received at least 1 dose of alisertib and have measurable disease at baseline and have at least 1 post baseline response assessment. |
| Arm/Group Title | Part 1: PIC Dose Escalation | Part 1: ECT Dose Escalation | Part 2: PTCL |
|---|---|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment. | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles). | Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). |
| Measure Participants | 23 | 23 | 1 |
| Number [percentage of participants] |
13
46.4%
|
9
32.1%
|
100
5000%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR is defined as the time from the date of first documentation of a response (either CR or PR) to the date of first documentation of progressive disease (PD) according to International Working Group (IWG) criteria. CR is defined as the disappearance of all evidence of disease and the definition for PR includes at least a 50% decrease in sum of the product of the diameters and no new lesions. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. |
| Time Frame | Baseline and every 2 cycles up to Month 12 until disease progression, 30 days after end of treatment (up to 422 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Response-Evaluable Population who had a response of CR or PR. |
| Arm/Group Title | Part 1: PIC Dose Escalation | Part 1: ECT Dose Escalation | Part 2: PTCL |
|---|---|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment. | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles). | Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). |
| Measure Participants | 3 | 2 | 1 |
| Median (Full Range) [months] |
0.03
|
2.07
|
0.03
|
| Title | Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 |
|---|---|
| Description | One peripheral blood sample (approximately 4 mL) was to be obtained on Day 1 of Cycle 1 prior to the first dose of alisertib to genotype participants for polymorphisms in UGT1A1 because UGT1A1 is one of the enzymes responsible for glucuronidation of alisertib, which is expected to contribute to the clearance of alisertib. wt=wild type. *28=polymorphism in the promoter region of a UGT1A1 allele resulting in reduced UGT1A1 expression. Not determined = blood sample was not evaluable. |
| Time Frame | Cycle 1 Day 1 predose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants who received any amount of study drug. Data is presented for one arm because the data was collected prior to the participant receiving their assigned treatment. |
| Arm/Group Title | Alisertib |
|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, PIC formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles) followed by alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles or alisertib 40 mg, ECT formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 58 |
| wt/wt |
23
82.1%
|
| wt/*28 |
23
82.1%
|
| *28/*28 |
8
28.6%
|
| other/other |
1
3.6%
|
| Not Determined |
2
7.1%
|
| Missing |
1
3.6%
|
| Title | Number of Participants With Polymorphisms in Aurora A Kinase |
|---|---|
| Description | |
| Time Frame | Cycle 1 Day 1 predose |
Outcome Measure Data
| Analysis Population Description |
|---|
| As per protocol amendment, no data was collected for polymorphisms in Aurora A Kinase. |
| Arm/Group Title | Alisertib |
|---|---|
| Arm/Group Description | Alisertib 25 or 35 mg, PIC formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles) followed by alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles or alisertib 40 mg, ECT formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose). |
| Measure Participants | 0 |
Adverse Events
| Time Frame | From first dose of study drug to 30 days after the last dose (up to 422 days) | |||||
|---|---|---|---|---|---|---|
| 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 | Part 1 PIC Dose Escalation | Part 1 ECT Dose Escalation | Part 2 PTCL | |||
| Arm/Group Description | Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment. | Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles). | Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). | |||
All Cause Mortality |
||||||
| Part 1 PIC Dose Escalation | Part 1 ECT Dose Escalation | Part 2 PTCL | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Part 1 PIC Dose Escalation | Part 1 ECT Dose Escalation | Part 2 PTCL | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/28 (42.9%) | 15/28 (53.6%) | 2/2 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 1/28 (3.6%) | 1 | 4/28 (14.3%) | 5 | 0/2 (0%) | 0 |
| Thrombocytopenia | 1/28 (3.6%) | 1 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Neutropenia | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Pancytopenia | 0/28 (0%) | 0 | 1/28 (3.6%) | 2 | 0/2 (0%) | 0 |
| Cardiac disorders | ||||||
| Bifascicular block | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Cardiac failure congestive | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Constipation | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Diarrhoea | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Small intestinal obstruction | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Stomatitis | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Abdominal pain | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| General disorders | ||||||
| Systemic inflammatory response syndrome | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Asthenia | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Pyrexia | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Infections and infestations | ||||||
| Septic shock | 1/28 (3.6%) | 1 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Staphylococcal infection | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Urinary tract infection | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia | 0/28 (0%) | 0 | 2/28 (7.1%) | 3 | 0/2 (0%) | 0 |
| Cellulitis | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Staphylococcal bacteraemia | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Herpes zoster | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Bronchitis | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Lung infection | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Hypercalcaemia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Musculoskeletal pain | 2/28 (7.1%) | 2 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Back pain | 1/28 (3.6%) | 1 | 1/28 (3.6%) | 2 | 0/2 (0%) | 0 |
| Flank pain | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Pathological fracture | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Pain in extremity | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Pain in jaw | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Lymphoma | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Plasma cell myeloma | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Nervous system disorders | ||||||
| Altered state of consciousness | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Psychiatric disorders | ||||||
| Confusional state | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Delirium | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Renal and urinary disorders | ||||||
| Renal failure | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Obstructive airways disorder | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Acute respiratory failure | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Respiratory failure | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis bullous | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Part 1 PIC Dose Escalation | Part 1 ECT Dose Escalation | Part 2 PTCL | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/28 (100%) | 28/28 (100%) | 2/2 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Neutropenia | 13/28 (46.4%) | 21 | 18/28 (64.3%) | 35 | 2/2 (100%) | 4 |
| Thrombocytopenia | 11/28 (39.3%) | 14 | 13/28 (46.4%) | 16 | 2/2 (100%) | 3 |
| Anaemia | 11/28 (39.3%) | 15 | 12/28 (42.9%) | 18 | 2/2 (100%) | 5 |
| Leukopenia | 4/28 (14.3%) | 7 | 11/28 (39.3%) | 22 | 0/2 (0%) | 0 |
| Lymphopenia | 2/28 (7.1%) | 3 | 6/28 (21.4%) | 9 | 0/2 (0%) | 0 |
| Leukocytosis | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Splenomegaly | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Cardiac disorders | ||||||
| Tachycardia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Ear and labyrinth disorders | 1/28 (3.6%) | 1 | 2/28 (7.1%) | 3 | 0/2 (0%) | 0 |
| Eye disorders | ||||||
| Eye disorders | 4/28 (14.3%) | 5 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Diarrhoea | 9/28 (32.1%) | 12 | 14/28 (50%) | 20 | 1/2 (50%) | 1 |
| Nausea | 11/28 (39.3%) | 13 | 9/28 (32.1%) | 10 | 0/2 (0%) | 0 |
| Vomiting | 6/28 (21.4%) | 7 | 6/28 (21.4%) | 8 | 0/2 (0%) | 0 |
| Constipation | 2/28 (7.1%) | 2 | 5/28 (17.9%) | 5 | 2/2 (100%) | 2 |
| Stomatitis | 3/28 (10.7%) | 3 | 2/28 (7.1%) | 2 | 2/2 (100%) | 2 |
| Dry mouth | 4/28 (14.3%) | 4 | 1/28 (3.6%) | 1 | 1/2 (50%) | 1 |
| Abdominal pain | 2/28 (7.1%) | 4 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Dyspepsia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Haemorrhoids | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Odynophagia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Oral pain | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| General disorders | ||||||
| Fatigue | 10/28 (35.7%) | 11 | 10/28 (35.7%) | 13 | 0/2 (0%) | 0 |
| Oedema peripheral | 2/28 (7.1%) | 2 | 1/28 (3.6%) | 1 | 1/2 (50%) | 1 |
| Chills | 4/28 (14.3%) | 5 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Pyrexia | 3/28 (10.7%) | 3 | 3/28 (10.7%) | 3 | 0/2 (0%) | 0 |
| Asthenia | 3/28 (10.7%) | 3 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Hyperbilirubinaemia | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Infections and infestations | ||||||
| Upper respiratory tract infection | 4/28 (14.3%) | 4 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Urinary tract infection | 0/28 (0%) | 0 | 3/28 (10.7%) | 6 | 1/2 (50%) | 1 |
| Influenza | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Oral candidiasis | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/28 (0%) | 0 | 1/28 (3.6%) | 1 | 1/2 (50%) | 1 |
| Fall | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Post-traumatic pain | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Investigations | ||||||
| Blood alkaline phosphatase increased | 2/28 (7.1%) | 2 | 3/28 (10.7%) | 3 | 0/2 (0%) | 0 |
| Blood bilirubin increased | 0/28 (0%) | 0 | 5/28 (17.9%) | 5 | 0/2 (0%) | 0 |
| White blood cell count decreased | 1/28 (3.6%) | 2 | 4/28 (14.3%) | 5 | 0/2 (0%) | 0 |
| Alanine aminotransferase increased | 1/28 (3.6%) | 1 | 3/28 (10.7%) | 3 | 0/2 (0%) | 0 |
| Aspartate aminotransferase increased | 1/28 (3.6%) | 1 | 3/28 (10.7%) | 4 | 0/2 (0%) | 0 |
| Blood creatinine increased | 2/28 (7.1%) | 2 | 1/28 (3.6%) | 1 | 1/2 (50%) | 1 |
| Blood lactate dehydrogenase increased | 1/28 (3.6%) | 1 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Nutritional condition abnormal | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Hypokalaemia | 3/28 (10.7%) | 3 | 7/28 (25%) | 8 | 2/2 (100%) | 2 |
| Decreased appetite | 6/28 (21.4%) | 6 | 4/28 (14.3%) | 4 | 1/2 (50%) | 1 |
| Hyponatraemia | 2/28 (7.1%) | 2 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Dehydration | 2/28 (7.1%) | 2 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Hypocalcaemia | 1/28 (3.6%) | 1 | 1/28 (3.6%) | 1 | 1/2 (50%) | 1 |
| Hypomagnesaemia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 1/2 (50%) | 1 |
| Hypophosphataemia | 0/28 (0%) | 0 | 3/28 (10.7%) | 3 | 0/2 (0%) | 0 |
| Hypercalcaemia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Hyperglycaemia | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Hyperuricaemia | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 | 1/2 (50%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/28 (7.1%) | 2 | 3/28 (10.7%) | 3 | 0/2 (0%) | 0 |
| Back pain | 3/28 (10.7%) | 3 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Bone pain | 2/28 (7.1%) | 2 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal pain | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Nervous system disorders | ||||||
| Somnolence | 2/28 (7.1%) | 2 | 6/28 (21.4%) | 6 | 1/2 (50%) | 1 |
| Dizziness | 0/28 (0%) | 0 | 4/28 (14.3%) | 5 | 1/2 (50%) | 1 |
| Headache | 2/28 (7.1%) | 2 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Tremor | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Psychiatric disorders | ||||||
| Insomnia | 3/28 (10.7%) | 3 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Anxiety | 1/28 (3.6%) | 1 | 1/28 (3.6%) | 1 | 1/2 (50%) | 1 |
| Depression | 3/28 (10.7%) | 3 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Confusional state | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Mental status changes | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Panic attack | 0/28 (0%) | 0 | 0/28 (0%) | 0 | 1/2 (50%) | 1 |
| Renal and urinary disorders | ||||||
| Renal and urinary disorders | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 7/28 (25%) | 7 | 4/28 (14.3%) | 5 | 0/2 (0%) | 0 |
| Dyspnoea | 6/28 (21.4%) | 6 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Rhinorrhoea | 2/28 (7.1%) | 2 | 1/28 (3.6%) | 1 | 0/2 (0%) | 0 |
| Dyspnoea exertional | 0/28 (0%) | 0 | 2/28 (7.1%) | 2 | 0/2 (0%) | 0 |
| Nasal congestion | 2/28 (7.1%) | 2 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Sinus congestion | 2/28 (7.1%) | 2 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 5/28 (17.9%) | 5 | 11/28 (39.3%) | 11 | 0/2 (0%) | 0 |
| Pruritus | 0/28 (0%) | 0 | 4/28 (14.3%) | 4 | 0/2 (0%) | 0 |
| Dermatitis | 2/28 (7.1%) | 3 | 0/28 (0%) | 0 | 0/2 (0%) | 0 |
| Vascular disorders | ||||||
| Hypotension | 3/28 (10.7%) | 3 | 2/28 (7.1%) | 3 | 0/2 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00697346
Other Study ID Numbers:
- C14003
- U1111-1187-1184
First Posted:
Jun 13, 2008
Last Update Posted:
May 31, 2019
Last Verified:
Feb 1, 2019