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MPACT Study to Compare Effects of Targeted Drugs on Tumor Gene Variations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01827384
Recruitment Status : Completed
First Posted : April 9, 2013
Results First Posted : May 10, 2022
Last Update Posted : May 10, 2022
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced Malignant Solid Neoplasm
Interventions Drug: Adavosertib
Drug: Carboplatin
Drug: Everolimus
Drug: Temozolomide
Drug: Trametinib
Drug: Veliparib
Enrollment 208
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
Hide Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated.
Period Title: Overall Study
Started 13 1 9 1 1 22 2 1 2 15 7 1 2 131
Completed 13 1 9 1 1 22 2 1 2 15 7 1 2 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 131
Reason Not Completed
Switched to alternative treatment             0             0             0             0             0             0             0             0             0             0             0             0             0             2
Disease progression before treatment             0             0             0             0             0             0             0             0             0             0             0             0             0             4
Ineligible             0             0             0             0             0             0             0             0             0             0             0             0             0             19
Participant died before treatment             0             0             0             0             0             0             0             0             0             0             0             0             0             5
Insufficient tumor cells             0             0             0             0             0             0             0             0             0             0             0             0             0             13
No actionable mutation             0             0             0             0             0             0             0             0             0             0             0             0             0             73
Participant declined to participate (before treatment started)             0             0             0             0             0             0             0             0             0             0             0             0             0             15
Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated Total
Hide Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated. Total of all reporting groups
Overall Number of Baseline Participants 13 1 9 1 1 22 2 1 2 15 7 1 2 131 208
Hide Baseline Analysis Population Description
Enrollment data was captured for 131 participants who signed consent and were enrolled but not treated.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  46.2%
1
 100.0%
6
  66.7%
1
 100.0%
1
 100.0%
13
  59.1%
2
 100.0%
1
 100.0%
2
 100.0%
11
  73.3%
3
  42.9%
1
 100.0%
2
 100.0%
89
  67.9%
139
  66.8%
>=65 years
7
  53.8%
0
   0.0%
3
  33.3%
0
   0.0%
0
   0.0%
9
  40.9%
0
   0.0%
0
   0.0%
0
   0.0%
4
  26.7%
4
  57.1%
0
   0.0%
0
   0.0%
42
  32.1%
69
  33.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
61  (15.15) 59  (0) 54  (15.15) 59.1  (0) 59  (0) 58  (12.22) 54  (9.9) 45  (0) 55.95  (7) 59  (10.54) 63.2  (13.72) 39  (0) 61.65  (4.03) 58  (11.53) 57.75  (11.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
Female
9
  69.2%
0
   0.0%
6
  66.7%
1
 100.0%
1
 100.0%
12
  54.5%
1
  50.0%
0
   0.0%
2
 100.0%
13
  86.7%
3
  42.9%
1
 100.0%
0
   0.0%
67
  51.1%
116
  55.8%
Male
4
  30.8%
1
 100.0%
3
  33.3%
0
   0.0%
0
   0.0%
10
  45.5%
1
  50.0%
1
 100.0%
0
   0.0%
2
  13.3%
4
  57.1%
0
   0.0%
2
 100.0%
64
  48.9%
92
  44.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
2
   9.1%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
0
   0.0%
11
   8.4%
15
   7.2%
Not Hispanic or Latino
13
 100.0%
1
 100.0%
8
  88.9%
1
 100.0%
1
 100.0%
19
  86.4%
2
 100.0%
1
 100.0%
2
 100.0%
14
  93.3%
7
 100.0%
1
 100.0%
2
 100.0%
117
  89.3%
189
  90.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   2.3%
4
   1.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
1
   0.5%
Asian
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
   4.5%
0
   0.0%
0
   0.0%
0
   0.0%
2
  13.3%
0
   0.0%
0
   0.0%
0
   0.0%
9
   6.9%
13
   6.3%
Native Hawaiian or Other Pacific Islander
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
Black or African American
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
  18.2%
0
   0.0%
0
   0.0%
0
   0.0%
2
  13.3%
2
  28.6%
0
   0.0%
0
   0.0%
19
  14.5%
28
  13.5%
White
11
  84.6%
1
 100.0%
8
  88.9%
1
 100.0%
1
 100.0%
15
  68.2%
2
 100.0%
1
 100.0%
2
 100.0%
9
  60.0%
5
  71.4%
1
 100.0%
2
 100.0%
95
  72.5%
154
  74.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
0
   0.0%
0
   0.0%
0
   0.0%
2
  13.3%
0
   0.0%
0
   0.0%
0
   0.0%
7
   5.3%
11
   5.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
13 1 9 1 1 22 2 1 2 15 7 1 2 131 208
Karnofsky Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
100
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
0
   0.0%
0
   0.0%
1
  50.0%
1
   6.7%
1
  14.3%
0
   0.0%
0
   0.0%
6
   4.6%
11
   5.3%
90
8
  61.5%
1
 100.0%
2
  22.2%
1
 100.0%
1
 100.0%
14
  63.6%
2
 100.0%
0
   0.0%
0
   0.0%
8
  53.3%
4
  57.1%
1
 100.0%
1
  50.0%
76
  58.0%
119
  57.2%
80
3
  23.1%
0
   0.0%
6
  66.7%
0
   0.0%
0
   0.0%
6
  27.3%
0
   0.0%
1
 100.0%
1
  50.0%
6
  40.0%
2
  28.6%
0
   0.0%
1
  50.0%
41
  31.3%
67
  32.2%
70
2
  15.4%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8
   6.1%
11
   5.3%
[1]
Measure Description: Karnofsky Performance Status 100 = Normal, no complaints, no evidence of disease. 90 = Able to carry on normal activity; minor signs or symptoms of disease. 80 = Normal activity with effort; some signs or symptoms of disease. 70 = Cares for self, unable to carry on normal activity or to do active work. 100 is a better outcome than 70.
Participants with an Actionable Mutation of Interest (aMOI) in a Targeted Pathway   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 1 participants 9 participants 1 participants 1 participants 22 participants 2 participants 1 participants 2 participants 15 participants 7 participants 1 participants 2 participants 131 participants 208 participants
Deoxyribonucleic acid (DNA) repair
9
  69.2%
1
 100.0%
5
  55.6%
0
   0.0%
0
   0.0%
4
  18.2%
1
  50.0%
1
 100.0%
1
  50.0%
11
  73.3%
7
 100.0%
0
   0.0%
1
  50.0%
21
  16.0%
62
  29.8%
P13K
1
   7.7%
0
   0.0%
4
  44.4%
0
   0.0%
1
 100.0%
1
   4.5%
0
   0.0%
0
   0.0%
0
   0.0%
3
  20.0%
0
   0.0%
1
 100.0%
0
   0.0%
4
   3.1%
15
   7.2%
RAS/RAF/MEK
3
  23.1%
0
   0.0%
0
   0.0%
1
 100.0%
0
   0.0%
17
  77.3%
1
  50.0%
0
   0.0%
1
  50.0%
1
   6.7%
0
   0.0%
0
   0.0%
1
  50.0%
13
   9.9%
38
  18.3%
No aMOI detected
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
93
  71.0%
93
  44.7%
[1]
Measure Description:

Reported for all participants with an aMOI (i.e. mutations of interest) detected. Participants with an aMOI in more than one pathway are counted here by mutation with highest frequency. Therefore, rows are mutually exclusive; a participant cannot be counted in more than 1 row.

PI3K - phosphoinositide 3-kinase RAF - rapidly accelerated fibrosarcoma RAS - rat sarcoma MEK - mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) No aMOI detected - Biopsy either was not collected, could not be analyzed, or did not have an aMOI detected.

1.Primary Outcome
Title Number of Participants With an Objective Response
Hide Description ORR is the proportion of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all tumors. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to 30 days after completion of study treatment, up to 75 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants enrolled but not treated were not applicable for this outcome measure.
Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3
Hide Arm/Group Description:
TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC2: Everolimus 10 mg by mouth (PO) every day (QD)
TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD)
TAC3: Trametinib 2mg by mouth (PO) every day (QD)
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD)
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD)
Overall Number of Participants Analyzed 13 1 9 1 1 22 2 1 2 15 7 1 2
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Partial Response
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title Proportion of Participants With 4 Month Progression-free Survival (PFS)
Hide Description Time from random assignment to progression or death from any cause (whichever comes first). Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions is also considered progressions.
Time Frame 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants enrolled but not treated were not applicable for this outcome measure.
Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3
Hide Arm/Group Description:
TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC2: Everolimus 10 mg by mouth (PO) every day (QD)
TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD)
TAC3: Trametinib 2mg by mouth (PO) every day (QD)
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD)
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD)
Overall Number of Participants Analyzed 13 1 9 1 1 22 2 1 2 15 7 1 2
Measure Type: Number
Unit of Measure: proportion of participants
0.23 0.00 0.22 0.00 1.00 0.41 0.50 0.00 0.00 0.13 0.29 0.00 0.00
3.Other Pre-specified Outcome
Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Hide Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approx. 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
Adverse events were collected for participants that were enrolled but not treated.
Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
Hide Arm/Group Description:
TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC2: Everolimus 10 mg by mouth (PO) every day (QD)
TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD)
TAC3: Trametinib 2mg by mouth (PO) every day (QD)
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD)
TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD)
Participants who signed consent and were enrolled but not treated.
Overall Number of Participants Analyzed 13 1 9 1 1 22 2 1 2 15 7 1 2 131
Measure Type: Count of Participants
Unit of Measure: Participants
13
 100.0%
1
 100.0%
9
 100.0%
1
 100.0%
1
 100.0%
22
 100.0%
2
 100.0%
1
 100.0%
2
 100.0%
15
 100.0%
7
 100.0%
1
 100.0%
2
 100.0%
2
   1.5%
Time Frame Date treatment consent signed to date off study, approximately 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
Hide Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated.
All-Cause Mortality
Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/13 (7.69%)      0/1 (0.00%)      3/9 (33.33%)      0/1 (0.00%)      0/1 (0.00%)      1/22 (4.55%)      0/2 (0.00%)      0/1 (0.00%)      0/2 (0.00%)      1/15 (6.67%)      1/7 (14.29%)      0/1 (0.00%)      0/2 (0.00%)      5/131 (3.82%)    
Hide Serious Adverse Events
Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/13 (38.46%)      0/1 (0.00%)      4/9 (44.44%)      1/1 (100.00%)      0/1 (0.00%)      11/22 (50.00%)      1/2 (50.00%)      1/1 (100.00%)      1/2 (50.00%)      10/15 (66.67%)      4/7 (57.14%)      1/1 (100.00%)      2/2 (100.00%)      10/131 (7.63%)    
Blood and lymphatic system disorders                             
Anemia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 1/2 (50.00%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 2/15 (13.33%)  3 1/7 (14.29%)  2 1/1 (100.00%)  1 1/2 (50.00%)  2 0/131 (0.00%)  0
Febrile neutropenia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 3/15 (20.00%)  3 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Endocrine disorders                             
Adrenal insufficiency  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Gastrointestinal disorders                             
Abdominal pain  1  1/13 (7.69%)  2 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 1/131 (0.76%)  1
Ascites  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Colitis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Colonic obstruction  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 1/2 (50.00%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Colonic perforation  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Constipation  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 0/131 (0.00%)  0
Diarrhea  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 1/2 (50.00%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 2/15 (13.33%)  2 0/7 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 0/131 (0.00%)  0
Ileus  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Nausea  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Rectal hemorrhage  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Small intestinal obstruction  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Small intestinal perforation  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Vomiting  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 1/2 (50.00%)  2 1/1 (100.00%)  1 0/2 (0.00%)  0 3/15 (20.00%)  3 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders                             
Death NOS  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Edema limbs  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Fever  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 2/22 (9.09%)  3 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Infusion related reaction  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Sudden death NOS  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Infections and infestations                             
Bronchial infection  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Lung infection  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  2 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Sepsis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 1/1 (100.00%)  1 1/2 (50.00%)  1 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 2/131 (1.53%)  3
Urinary tract infection  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  2 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Injury, poisoning and procedural complications                             
Hip fracture  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  2 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Postoperative hemorrhage  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Investigations                             
Alanine aminotransferase increased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Alkaline phosphatase increased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Aspartate aminotransferase increased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 2/22 (9.09%)  3 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 2/131 (1.53%)  2
Blood bilirubin increased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Neutrophil count decreased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 1/15 (6.67%)  1 2/7 (28.57%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Platelet count decreased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 3/15 (20.00%)  3 0/7 (0.00%)  0 1/1 (100.00%)  1 1/2 (50.00%)  2 0/131 (0.00%)  0
White blood cell decreased  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  2 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Metabolism and nutrition disorders                             
Dehydration  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 1/2 (50.00%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Hyperkalemia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/131 (0.00%)  0
Hypoglycemia  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Hypokalemia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Hypomagnesemia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/131 (0.00%)  0
Hyponatremia  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 1/7 (14.29%)  1 0/1 (0.00%)  0 1/2 (50.00%)  1 1/131 (0.76%)  1
Hypophosphatemia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Musculoskeletal and connective tissue disorders                             
Back pain  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Muscle weakness right-sided  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                             
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, CNS Metastasis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Progressive disease  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Nervous system disorders                             
Dizziness  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Presyncope  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Syncope  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Renal and urinary disorders                             
Acute kidney injury  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 1/15 (6.67%)  1 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Renal and urinary disorders - Other, Urinary tract obstruction  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Renal and urinary disorders - Other, ureter obstruction  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Urinary tract obstruction  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                             
Cough  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Dyspnea  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 3/22 (13.64%)  3 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 2/131 (1.53%)  2
Hypoxia  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Laryngeal hemorrhage  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Pleural effusion  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Pneumothorax  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Respiratory, thoracic and mediastinal disorders - Other, Shortness of breath  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Vascular disorders                             
Hypertension  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 2/22 (9.09%)  2 1/2 (50.00%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Hypotension  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 1/131 (0.76%)  1
Thromboembolic event  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/13 (100.00%)      1/1 (100.00%)      9/9 (100.00%)      1/1 (100.00%)      1/1 (100.00%)      22/22 (100.00%)      2/2 (100.00%)      1/1 (100.00%)      2/2 (100.00%)      15/15 (100.00%)      7/7 (100.00%)      1/1 (100.00%)      2/2 (100.00%)      2/131 (1.53%)    
Blood and lymphatic system disorders                             
Anemia  1  5/13 (38.46%)  13 0/1 (0.00%)  0 3/9 (33.33%)  7 1/1 (100.00%)  3 0/1 (0.00%)  0 9/22 (40.91%)  26 1/2 (50.00%)  3 1/1 (100.00%)  1 1/2 (50.00%)  6 10/15 (66.67%)  23 6/7 (85.71%)  27 1/1 (100.00%)  3 2/2 (100.00%)  9 2/131 (1.53%)  5
Hemolysis  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Thrombotic thrombocytopenic purpura  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Cardiac disorders                             
Atrial fibrillation  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Electrocardiogram QT corrected interval prolonged  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Palpitations  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Sinus bradycardia  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 3/22 (13.64%)  4 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Sinus tachycardia  1  3/13 (23.08%)  5 0/1 (0.00%)  0 1/9 (11.11%)  1 1/1 (100.00%)  2 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 1/15 (6.67%)  1 1/7 (14.29%)  1 1/1 (100.00%)  1 0/2 (0.00%)  0 1/131 (0.76%)  1
Endocrine disorders                             
Hypothyroidism  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Eye disorders                             
Conjunctivitis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Corneal ulcer  1  0/13 (0.00%)  0 1/1 (100.00%)  2 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Dry eye  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Eye disorders - Other, Blepharitis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/131 (0.00%)  0
Eye disorders - Other, Peripheral shadow  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Glaucoma  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Watering eyes  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Gastrointestinal disorders                             
Abdominal distension  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Abdominal pain  1  4/13 (30.77%)  5 1/1 (100.00%)  3 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 4/22 (18.18%)  4 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 1/2 (50.00%)  1 1/131 (0.76%)  2
Ascites  1  1/13 (7.69%)  1 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 1/1 (100.00%)  1 1/2 (50.00%)  1 0/131 (0.00%)  0
Bloating  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Cheilitis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Constipation  1  7/13 (53.85%)  8 1/1 (100.00%)  2 4/9 (44.44%)  4 1/1 (100.00%)  1 0/1 (0.00%)  0 6/22 (27.27%)  7 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 3/15 (20.00%)  3 5/7 (71.43%)  5 0/1 (0.00%)  0 1/2 (50.00%)  1 0/131 (0.00%)  0
Diarrhea  1  4/13 (30.77%)  4 1/1 (100.00%)  4 2/9 (22.22%)  2 0/1 (0.00%)  0 1/1 (100.00%)  1 11/22 (50.00%)  16 2/2 (100.00%)  4 1/1 (100.00%)  1 2/2 (100.00%)  4 7/15 (46.67%)  10 6/7 (85.71%)  10 1/1 (100.00%)  1 1/2 (50.00%)  2 0/131 (0.00%)  0
Dry mouth  1  0/13 (0.00%)  0 0/1 (0.00%)  0 2/9 (22.22%)  2 0/1 (0.00%)  0 0/1 (0.00%)  0 3/22 (13.64%)  3 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Dyspepsia  1  1/13 (7.69%)  1 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 3/7 (42.86%)  4 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Gastroesophageal reflux disease  1  2/13 (15.38%)  2 0/1 (0.00%)  0 2/9 (22.22%)  2 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 0/131 (0.00%)  0
Gastrointestinal pain  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  2 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Lower gastrointestinal hemorrhage  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Mucositis oral  1  1/13 (7.69%)  1 0/1 (0.00%)  0 3/9 (33.33%)  4 0/1 (0.00%)  0 1/1 (100.00%)  2 2/22 (9.09%)  3 0/2 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 1/2 (50.00%)  1 0/131 (0.00%)  0
Nausea  1  9/13 (69.23%)  14 0/1 (0.00%)  0 4/9 (44.44%)  4 1/1 (100.00%)  1 1/1 (100.00%)  1 11/22 (50.00%)  14 0/2 (0.00%)  0 1/1 (100.00%)  1 2/2 (100.00%)  3 11/15 (73.33%)  20 5/7 (71.43%)  10 0/1 (0.00%)  0 2/2 (100.00%)  2 1/131 (0.76%)  1
Rectal hemorrhage  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Vomiting  1  8/13 (61.54%)  15 0/1 (0.00%)  0 3/9 (33.33%)  3 0/1 (0.00%)  0 1/1 (100.00%)  1 6/22 (27.27%)  11 1/2 (50.00%)  1 1/1 (100.00%)  1 2/2 (100.00%)  3 8/15 (53.33%)  9 4/7 (57.14%)  10 1/1 (100.00%)  1 0/2 (0.00%)  0 1/131 (0.76%)  1
General disorders                             
Chills  1  1/13 (7.69%)  1 1/1 (100.00%)  1 3/9 (33.33%)  4 0/1 (0.00%)  0 0/1 (0.00%)  0 4/22 (18.18%)  5 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Edema limbs  1  1/13 (7.69%)  2 0/1 (0.00%)  0 4/9 (44.44%)  6 1/1 (100.00%)  1 0/1 (0.00%)  0 7/22 (31.82%)  12 1/2 (50.00%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 2/7 (28.57%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Edema trunk  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Fatigue  1  8/13 (61.54%)  11 1/1 (100.00%)  4 4/9 (44.44%)  4 0/1 (0.00%)  0 1/1 (100.00%)  1 10/22 (45.45%)  16 1/2 (50.00%)  1 1/1 (100.00%)  2 2/2 (100.00%)  4 9/15 (60.00%)  12 4/7 (57.14%)  4 0/1 (0.00%)  0 1/2 (50.00%)  1 0/131 (0.00%)  0
Fever  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 3/22 (13.64%)  4 0/2 (0.00%)  0 1/1 (100.00%)  1 1/2 (50.00%)  2 2/15 (13.33%)  3 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/131 (0.76%)  1
Flu like symptoms  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 1/7 (14.29%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, Edema Limbs  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, GERD  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 1/15 (6.67%)  1 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, Hand and Foot Syndrome  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/22 (4.55%)  1 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, cellulitis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, cellulitits  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, cellutitis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, neutrophilic dermatoses  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
General disorders and administration site conditions - Other, neutrophilic dermatosis  1  0/13 (0.00%)  0 0/1 (0.00%)  0 1/9 (11.11%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/15 (0.00%)  0 0/7 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/131 (0.00%)  0
Infusion related reaction  1  0/13 (0.00%)  0 0/1 (0.00%)  0 0/9 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/22 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0