Trial Outcomes & Findings for Alisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer (NCT NCT02860000)
NCT ID: NCT02860000
Last Updated: 2025-12-30
Results Overview
For arm I, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with alisertib monotherapy divided by the number of patients who started alisertib monotherapy. For arm II, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with combination of alisertib and fulvestrant divided by the number of patients who started treatment with the combination of a
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
96 participants
Primary outcome timeframe
Up to 4.5 years
Results posted on
2025-12-30
Participant Flow
Participant milestones
| Measure |
Arm I (Alisertib)
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
\>
\> Alisertib: Given PO
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
\>
\> Alisertib: Given PO
\>
\> Fulvestrant: Given IM
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Initial Treatment
STARTED
|
47
|
49
|
|
Initial Treatment
COMPLETED
|
46
|
45
|
|
Initial Treatment
NOT COMPLETED
|
1
|
4
|
|
Optional Cross-over
STARTED
|
17
|
0
|
|
Optional Cross-over
COMPLETED
|
17
|
0
|
|
Optional Cross-over
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Alisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer
Baseline characteristics by cohort
| Measure |
Arm I (Alisertib)
n=46 Participants
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.\> \> Alisertib: Given PO\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=45 Participants
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.\>
\> Alisertib: Given PO\>
\> Fulvestrant: Given IM\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Total
n=91 Participants
Total of all reporting groups
|
|---|---|---|---|
|
ER status
Negative
|
5 Participants
n=174 Participants
|
1 Participants
n=166 Participants
|
6 Participants
n=167 Participants
|
|
ER status
Positive
|
41 Participants
n=174 Participants
|
44 Participants
n=166 Participants
|
85 Participants
n=167 Participants
|
|
Age, Customized
<40 (Years)
|
3 Participants
n=174 Participants
|
4 Participants
n=166 Participants
|
7 Participants
n=167 Participants
|
|
Age, Customized
40-59 (Years)
|
14 Participants
n=174 Participants
|
20 Participants
n=166 Participants
|
34 Participants
n=167 Participants
|
|
Age, Customized
60-74 (Years)
|
25 Participants
n=174 Participants
|
19 Participants
n=166 Participants
|
44 Participants
n=167 Participants
|
|
Age, Customized
75+ (Years)
|
4 Participants
n=174 Participants
|
2 Participants
n=166 Participants
|
6 Participants
n=167 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=174 Participants
|
45 Participants
n=166 Participants
|
91 Participants
n=167 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=174 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=167 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=174 Participants
|
4 Participants
n=166 Participants
|
5 Participants
n=167 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
45 Participants
n=174 Participants
|
41 Participants
n=166 Participants
|
86 Participants
n=167 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=174 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=167 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=174 Participants
|
1 Participants
n=166 Participants
|
1 Participants
n=167 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=174 Participants
|
0 Participants
n=166 Participants
|
2 Participants
n=167 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=174 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=167 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=174 Participants
|
3 Participants
n=166 Participants
|
6 Participants
n=167 Participants
|
|
Race (NIH/OMB)
White
|
41 Participants
n=174 Participants
|
39 Participants
n=166 Participants
|
80 Participants
n=167 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=174 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=167 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=174 Participants
|
2 Participants
n=166 Participants
|
2 Participants
n=167 Participants
|
|
BMI Group
Underweight
|
0 Participants
n=174 Participants
|
1 Participants
n=166 Participants
|
1 Participants
n=167 Participants
|
|
BMI Group
Normal
|
14 Participants
n=174 Participants
|
21 Participants
n=166 Participants
|
35 Participants
n=167 Participants
|
|
BMI Group
Overweight
|
13 Participants
n=174 Participants
|
15 Participants
n=166 Participants
|
28 Participants
n=167 Participants
|
|
BMI Group
Obese
|
19 Participants
n=174 Participants
|
8 Participants
n=166 Participants
|
27 Participants
n=167 Participants
|
|
ECOG Performance Status
0
|
30 Participants
n=174 Participants
|
27 Participants
n=166 Participants
|
57 Participants
n=167 Participants
|
|
ECOG Performance Status
1
|
16 Participants
n=174 Participants
|
18 Participants
n=166 Participants
|
34 Participants
n=167 Participants
|
|
Prior Taxane Based Therapy
No
|
22 Participants
n=174 Participants
|
21 Participants
n=166 Participants
|
43 Participants
n=167 Participants
|
|
Prior Taxane Based Therapy
Yes
|
24 Participants
n=174 Participants
|
24 Participants
n=166 Participants
|
48 Participants
n=167 Participants
|
|
Prior Anthracycline Based Therapy
No
|
29 Participants
n=174 Participants
|
23 Participants
n=166 Participants
|
52 Participants
n=167 Participants
|
|
Prior Anthracycline Based Therapy
Yes
|
17 Participants
n=174 Participants
|
22 Participants
n=166 Participants
|
39 Participants
n=167 Participants
|
|
Prior Capecitabine Regimen
No
|
42 Participants
n=174 Participants
|
42 Participants
n=166 Participants
|
84 Participants
n=167 Participants
|
|
Prior Capecitabine Regimen
Yes
|
4 Participants
n=174 Participants
|
3 Participants
n=166 Participants
|
7 Participants
n=167 Participants
|
|
Prior Chemotherapy
No
|
39 Participants
n=174 Participants
|
41 Participants
n=166 Participants
|
80 Participants
n=167 Participants
|
|
Prior Chemotherapy
Yes
|
7 Participants
n=174 Participants
|
4 Participants
n=166 Participants
|
11 Participants
n=167 Participants
|
|
Prior Systemic Chemotherapy
No
|
24 Participants
n=174 Participants
|
14 Participants
n=166 Participants
|
38 Participants
n=167 Participants
|
|
Prior Systemic Chemotherapy
Yes
|
22 Participants
n=174 Participants
|
31 Participants
n=166 Participants
|
53 Participants
n=167 Participants
|
|
Prior Anastrozole Endocrine Therapy
No
|
30 Participants
n=174 Participants
|
31 Participants
n=166 Participants
|
61 Participants
n=167 Participants
|
|
Prior Anastrozole Endocrine Therapy
Yes
|
16 Participants
n=174 Participants
|
14 Participants
n=166 Participants
|
30 Participants
n=167 Participants
|
|
Prior Tamoxifen Treatment
No
|
31 Participants
n=174 Participants
|
23 Participants
n=166 Participants
|
54 Participants
n=167 Participants
|
|
Prior Tamoxifen Treatment
Yes
|
15 Participants
n=174 Participants
|
22 Participants
n=166 Participants
|
37 Participants
n=167 Participants
|
|
Prior Fulvestrant Treatment
No
|
40 Participants
n=174 Participants
|
43 Participants
n=166 Participants
|
83 Participants
n=167 Participants
|
|
Prior Fulvestrant Treatment
Yes
|
6 Participants
n=174 Participants
|
2 Participants
n=166 Participants
|
8 Participants
n=167 Participants
|
|
Prior Endocrine Therapy
No
|
19 Participants
n=174 Participants
|
10 Participants
n=166 Participants
|
29 Participants
n=167 Participants
|
|
Prior Endocrine Therapy
Yes
|
27 Participants
n=174 Participants
|
35 Participants
n=166 Participants
|
62 Participants
n=167 Participants
|
|
Prior Exemestane Therapy
No
|
30 Participants
n=174 Participants
|
19 Participants
n=166 Participants
|
49 Participants
n=167 Participants
|
|
Prior Exemestane Therapy
Yes
|
16 Participants
n=174 Participants
|
26 Participants
n=166 Participants
|
42 Participants
n=167 Participants
|
|
Prior Fulvestrant Therapy
No
|
1 Participants
n=174 Participants
|
9 Participants
n=166 Participants
|
10 Participants
n=167 Participants
|
|
Prior Fulvestrant Therapy
Yes
|
45 Participants
n=174 Participants
|
45 Participants
n=166 Participants
|
90 Participants
n=167 Participants
|
|
Prior Biologic Therapy
No
|
27 Participants
n=174 Participants
|
27 Participants
n=166 Participants
|
54 Participants
n=167 Participants
|
|
Prior Biologic Therapy
Yes
|
19 Participants
n=174 Participants
|
18 Participants
n=166 Participants
|
37 Participants
n=167 Participants
|
|
Prior Everolimus Therapy
No
|
29 Participants
n=174 Participants
|
19 Participants
n=166 Participants
|
48 Participants
n=167 Participants
|
|
Prior Everolimus Therapy
Yes
|
17 Participants
n=174 Participants
|
26 Participants
n=166 Participants
|
43 Participants
n=167 Participants
|
|
Clinical Resistance to Endocrine Therapy
Primary endocrine resistance
|
11 Participants
n=174 Participants
|
8 Participants
n=166 Participants
|
19 Participants
n=167 Participants
|
|
Clinical Resistance to Endocrine Therapy
Secondary endocrine resistance
|
35 Participants
n=174 Participants
|
37 Participants
n=166 Participants
|
72 Participants
n=167 Participants
|
|
ER findings from registration biopsy
ER positive (>= 10% staining)
|
40 Participants
n=174 Participants
|
39 Participants
n=166 Participants
|
79 Participants
n=167 Participants
|
|
ER findings from registration biopsy
ER weakly positive (1 to 9.9% staining) or ER negative (0% staining)
|
6 Participants
n=174 Participants
|
6 Participants
n=166 Participants
|
12 Participants
n=167 Participants
|
|
Bone Metastatic Disease
Yes
|
40 Participants
n=174 Participants
|
39 Participants
n=166 Participants
|
79 Participants
n=167 Participants
|
|
Bone Metastatic Disease
No
|
6 Participants
n=174 Participants
|
6 Participants
n=166 Participants
|
12 Participants
n=167 Participants
|
|
Liver Metastatic Disease
Yes
|
32 Participants
n=174 Participants
|
35 Participants
n=166 Participants
|
67 Participants
n=167 Participants
|
|
Liver Metastatic Disease
No
|
14 Participants
n=174 Participants
|
10 Participants
n=166 Participants
|
24 Participants
n=167 Participants
|
|
Nodal Metastatic Disease
Yes
|
25 Participants
n=174 Participants
|
22 Participants
n=166 Participants
|
47 Participants
n=167 Participants
|
|
Nodal Metastatic Disease
No
|
21 Participants
n=174 Participants
|
23 Participants
n=166 Participants
|
44 Participants
n=167 Participants
|
PRIMARY outcome
Timeframe: Up to 4.5 yearsFor arm I, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with alisertib monotherapy divided by the number of patients who started alisertib monotherapy. For arm II, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with combination of alisertib and fulvestrant divided by the number of patients who started treatment with the combination of a
Outcome measures
| Measure |
Arm I (Alisertib)
n=46 Participants
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
\>
\> Alisertib: Given PO
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=45 Participants
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
\>
\> Alisertib: Given PO
\>
\> Fulvestrant: Given IM
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Tumor Response Rate Defined as 100% Times the Number of Patients Who Meet the Criteria for Complete Response (CR) or Partial Response (PR) Using RECIST Criteria Version 1.1
|
19.6 Percentage of Participants
Interval 10.6 to 31.7
|
29.9 Percentage of Participants
Interval 19.9 to 32.3
|
SECONDARY outcome
Timeframe: Up to 4 weeksSpearman rank correlation coefficient will be used to examine the association between ER alpha expression and the biomarkers: CD44, CD24, total and phosphorylated expression of AURKA, SMAD5, and SOX2. A two sample test of the difference in proportions will be used to examine whether weak or no phosphorylated expression of AURKA, SMAD5, and SOX2 after one cycle of alisertib is associated with clinical benefit (CR + PR + stable disease on treatment for at least 6 months).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to 28 daysPercent change in CTC expression of aurora A kinase, ER, and phospho- SOX2 expression from pre-treatment levels will be determined for each patient. Bland-Altman plots and weighted kappa statistics will be used to examine the concordance between the percent change in aurora A kinase, ER, and phospho-SOX2 expression from pre-treatment levels in CTC and in tumor tissue.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to 28 daysSpearman rank correlation coefficient will be used to examine the association of maximum percentage of tumor shrinkage during treatment with the percent change after 1 cycle of treatment in aurora A Kinase (AAK) expressing cells, as well as percent changes after 1 cycle of treatment in tissue ER alpha, SMAD5, SOX2 expression and phosphorylation.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 24 weeksFor initial treatment in each arm, the CBR at 24 weeks will be defined as the proportion of patients who completed 6 cycles of treatment without documentation of disease progression. A 90% confidence interval for the CBR will be constructed using the Duffy-Santner approach to take into account the sequential nature of the study design.
Outcome measures
| Measure |
Arm I (Alisertib)
n=46 Participants
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
\>
\> Alisertib: Given PO
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=45 Participants
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
\>
\> Alisertib: Given PO
\>
\> Fulvestrant: Given IM
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Clinical Benefit Rate (CBR) During Initial Treatment Defined as Percentage of Patients Who Completed 6 Courses of Treatment Without Documentation of Disease Progression
|
41.3 percentage of participants
Interval 29.0 to 54.5
|
28.9 percentage of participants
Interval 18.0 to 42.0
|
SECONDARY outcome
Timeframe: Up to about 5 yearsWill be estimated using the Kaplan-Meier method.
Outcome measures
| Measure |
Arm I (Alisertib)
n=46 Participants
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
\>
\> Alisertib: Given PO
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=45 Participants
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
\>
\> Alisertib: Given PO
\>
\> Fulvestrant: Given IM
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Duration of Response Defined as Time From Randomization to Disease Progression Among Those Patients Whose Disease Meets the RECIST Criteria for CR or PR on 2 Consecutive Evaluations Approximately 8 Weeks Apart During Initial Treatment
|
465 days
Interval 113.0 to 1031.0
|
259.5 days
Interval 53.0 to 1863.0
|
SECONDARY outcome
Timeframe: Up to 30 days after last administration of study drugThe CTCAE version 4.0 will be used to grade and assign attribution to each adverse event reported during initial treatment and crossover treatment separately.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 5 yearsWill be estimated using the Kaplan-Meier method.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from randomization to the first of these disease events: local/regional or distant breast recurrence, DCIS or invasive breast disease in contralateral breast, non-breast second primary, or death due to any cause, assessed up to 5 yearsWill be estimated using the Kaplan-Meier method.
Outcome measures
| Measure |
Arm I (Alisertib)
n=46 Participants
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
\>
\> Alisertib: Given PO
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=45 Participants
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
\>
\> Alisertib: Given PO
\>
\> Fulvestrant: Given IM
\>
\> Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Progression-free Survival
|
5.6 months
Interval 3.9 to 10.0
|
5.4 months
Interval 3.0 to 7.8
|
Adverse Events
Arm I (Alisertib)
Serious events: 12 serious events
Other events: 45 other events
Deaths: 2 deaths
Arm II (Alisertib, Fulvestrant)
Serious events: 12 serious events
Other events: 47 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Arm I (Alisertib)
n=46 participants at risk
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=48 participants at risk
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
8.7%
4/46 • Number of events 5 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
4.2%
2/48 • Number of events 2 • Up to 5 years
|
|
Cardiac disorders
Acute coronary syndrome
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Cardiac disorders
Atrial fibrillation
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Cardiac disorders
Cardiac arrest
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Cardiac disorders
Heart failure
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Cardiac disorders
Mitral valve disease
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Diarrhea
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Mucositis oral
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
General disorders
Flu like symptoms
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Urinary tract infection
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Alanine aminotransferase increased
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
4.2%
2/48 • Number of events 2 • Up to 5 years
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Aspartate aminotransferase increased
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
4.2%
2/48 • Number of events 2 • Up to 5 years
|
|
Investigations
Blood bilirubin increased
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Ejection fraction decreased
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Investigations
Investigations - Other, specify
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Neutrophil count decreased
|
6.5%
3/46 • Number of events 7 • Up to 5 years
|
8.3%
4/48 • Number of events 4 • Up to 5 years
|
|
Investigations
Platelet count decreased
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
4.2%
2/48 • Number of events 2 • Up to 5 years
|
|
Investigations
White blood cell decreased
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
6.2%
3/48 • Number of events 3 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
2.1%
1/48 • Number of events 3 • Up to 5 years
|
|
Nervous system disorders
Edema cerebral
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Nervous system disorders
Headache
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Lethargy
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Somnolence
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Renal and urinary disorders
Acute kidney injury
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Vascular disorders
Hypotension
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
Other adverse events
| Measure |
Arm I (Alisertib)
n=46 participants at risk
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Alisertib, Fulvestrant)
n=48 participants at risk
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Investigations
Lymphocyte count increased
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Neutrophil count decreased
|
65.2%
30/46 • Number of events 169 • Up to 5 years
|
60.4%
29/48 • Number of events 117 • Up to 5 years
|
|
Investigations
Platelet count decreased
|
32.6%
15/46 • Number of events 93 • Up to 5 years
|
31.2%
15/48 • Number of events 140 • Up to 5 years
|
|
Investigations
Weight loss
|
0.00%
0/46 • Up to 5 years
|
4.2%
2/48 • Number of events 7 • Up to 5 years
|
|
Investigations
White blood cell decreased
|
60.9%
28/46 • Number of events 189 • Up to 5 years
|
60.4%
29/48 • Number of events 178 • Up to 5 years
|
|
Metabolism and nutrition disorders
Anorexia
|
41.3%
19/46 • Number of events 100 • Up to 5 years
|
39.6%
19/48 • Number of events 46 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.2%
1/46 • Number of events 3 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
4.2%
2/48 • Number of events 2 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.3%
2/46 • Number of events 8 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
4/46 • Number of events 4 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/46 • Up to 5 years
|
10.4%
5/48 • Number of events 6 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Dizziness
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Nervous system disorders
Hypersomnia
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Memory impairment
|
2.2%
1/46 • Number of events 3 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Nervous system disorders
Paresthesia
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Nervous system disorders
Peripheral motor neuropathy
|
4.3%
2/46 • Number of events 5 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Nervous system disorders
Somnolence
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 3 • Up to 5 years
|
|
Psychiatric disorders
Anxiety
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Psychiatric disorders
Confusion
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
2.1%
1/48 • Number of events 3 • Up to 5 years
|
|
Psychiatric disorders
Depression
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Psychiatric disorders
Insomnia
|
2.2%
1/46 • Number of events 4 • Up to 5 years
|
4.2%
2/48 • Number of events 5 • Up to 5 years
|
|
Renal and urinary disorders
Acute kidney injury
|
15.2%
7/46 • Number of events 59 • Up to 5 years
|
2.1%
1/48 • Number of events 5 • Up to 5 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Oth spec
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Renal and urinary disorders
Urinary incontinence
|
2.2%
1/46 • Number of events 40 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Reproductive system and breast disorders
Vaginal dryness
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Reproductive system and breast disorders
Vaginal inflammation
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.3%
2/46 • Number of events 5 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.5%
3/46 • Number of events 8 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
43.5%
20/46 • Number of events 244 • Up to 5 years
|
43.8%
21/48 • Number of events 128 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.3%
2/46 • Number of events 5 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrm
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
4.3%
2/46 • Number of events 4 • Up to 5 years
|
4.2%
2/48 • Number of events 6 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
6.5%
3/46 • Number of events 20 • Up to 5 years
|
12.5%
6/48 • Number of events 10 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcut tissue disord - Oth spec
|
4.3%
2/46 • Number of events 3 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Social circumstances
Social circumstances - Other, specify
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Surgical and medical procedures
Surgical and medical proced - Oth spec
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Vascular disorders
Hypertension
|
2.2%
1/46 • Number of events 18 • Up to 5 years
|
8.3%
4/48 • Number of events 12 • Up to 5 years
|
|
Vascular disorders
Lymphedema
|
0.00%
0/46 • Up to 5 years
|
4.2%
2/48 • Number of events 3 • Up to 5 years
|
|
Vascular disorders
Thromboembolic event
|
2.2%
1/46 • Number of events 40 • Up to 5 years
|
6.2%
3/48 • Number of events 13 • Up to 5 years
|
|
Gastrointestinal disorders
Mucositis oral
|
41.3%
19/46 • Number of events 59 • Up to 5 years
|
31.2%
15/48 • Number of events 34 • Up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
37.0%
17/46 • Number of events 80 • Up to 5 years
|
45.8%
22/48 • Number of events 95 • Up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
13.0%
6/46 • Number of events 18 • Up to 5 years
|
31.2%
15/48 • Number of events 46 • Up to 5 years
|
|
General disorders
Edema face
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
General disorders
Edema limbs
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
General disorders
Fatigue
|
89.1%
41/46 • Number of events 365 • Up to 5 years
|
83.3%
40/48 • Number of events 236 • Up to 5 years
|
|
General disorders
Flu like symptoms
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
General disorders
Gen disord and admin site conds-Oth spec
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
General disorders
Injection site reaction
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
10.4%
5/48 • Number of events 8 • Up to 5 years
|
|
General disorders
Pain
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Appendicitis
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Eye infection
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Infections and infestations
Infections and infestations - Oth spec
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Lymphocyte count decreased
|
15.2%
7/46 • Number of events 80 • Up to 5 years
|
27.1%
13/48 • Number of events 110 • Up to 5 years
|
|
Infections and infestations
Skin infection
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Infections and infestations
Upper respiratory infection
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
4.2%
2/48 • Number of events 3 • Up to 5 years
|
|
Infections and infestations
Urinary tract infection
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Injury, poisoning and procedural complications
Fall
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 3 • Up to 5 years
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Investigations
Alanine aminotransferase increased
|
4.3%
2/46 • Number of events 2 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Alkaline phosphatase increased
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
8.3%
4/48 • Number of events 10 • Up to 5 years
|
|
Investigations
Aspartate aminotransferase increased
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
12.5%
6/48 • Number of events 6 • Up to 5 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Investigations
Creatinine increased
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Investigations
Ejection fraction decreased
|
2.2%
1/46 • Number of events 14 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Investigations
Investigations - Other, specify
|
2.2%
1/46 • Number of events 11 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Dysphagia
|
2.2%
1/46 • Number of events 4 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Esophagitis
|
2.2%
1/46 • Number of events 10 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Gastritis
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
6.5%
3/46 • Number of events 6 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
2.2%
1/46 • Number of events 3 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Blood and lymphatic system disorders
Anemia
|
73.9%
34/46 • Number of events 310 • Up to 5 years
|
62.5%
30/48 • Number of events 192 • Up to 5 years
|
|
Cardiac disorders
Mitral valve disease
|
2.2%
1/46 • Number of events 3 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Ear and labyrinth disorders
Hearing impaired
|
2.2%
1/46 • Number of events 4 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Eye disorders
Blurred vision
|
4.3%
2/46 • Number of events 6 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Eye disorders
Dry eye
|
2.2%
1/46 • Number of events 2 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Eye disorders
Retinal detachment
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
1/46 • Number of events 1 • Up to 5 years
|
0.00%
0/48 • Up to 5 years
|
|
Gastrointestinal disorders
Anal ulcer
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/46 • Up to 5 years
|
2.1%
1/48 • Number of events 2 • Up to 5 years
|
|
Gastrointestinal disorders
Constipation
|
4.3%
2/46 • Number of events 3 • Up to 5 years
|
2.1%
1/48 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
23/46 • Number of events 184 • Up to 5 years
|
39.6%
19/48 • Number of events 119 • Up to 5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place