Trial Outcomes & Findings for Sorafenib Tosylate and Temsirolimus in Treating Patients With Recurrent Glioblastoma (NCT NCT00329719)
NCT ID: NCT00329719
Last Updated: 2018-10-16
Results Overview
The primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation. If more than 41 evaluable patients are accrued in group 1 or group 3, the additional patients will not be used to evaluate the decision rule for that group or otherwise used in any decision-making processes. However, they will be included in the final point and confidence interval estimates for that group. The 'success' probability, i.e., 6-month progression-free survival percentage, for each of group 1 and group 3 will be estimated as the number of evaluable patients still alive at 6 months divided by the total number of evaluable patients followed for at least 6 months. Ninety-five percent confidence intervals for the 'success' probability will be calculated according to the approach of Duffy and Santner. Progression is defined as a 25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
115 participants
Primary outcome timeframe
At 6 months
Results posted on
2018-10-16
Participant Flow
Participant milestones
| Measure |
Phase I, Arm A
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
49
|
9
|
45
|
|
Overall Study
COMPLETED
|
12
|
49
|
9
|
44
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Phase I, Arm A
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Sorafenib Tosylate and Temsirolimus in Treating Patients With Recurrent Glioblastoma
Baseline characteristics by cohort
| Measure |
Phase I, Arm A
n=12 Participants
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=49 Participants
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
n=9 Participants
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
n=45 Participants
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Total
n=115 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
53.8 years
n=5 Participants
|
55.5 years
n=7 Participants
|
58.4 years
n=5 Participants
|
56.8 years
n=4 Participants
|
56.0 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
37 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
110 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: At 6 monthsThe primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation. If more than 41 evaluable patients are accrued in group 1 or group 3, the additional patients will not be used to evaluate the decision rule for that group or otherwise used in any decision-making processes. However, they will be included in the final point and confidence interval estimates for that group. The 'success' probability, i.e., 6-month progression-free survival percentage, for each of group 1 and group 3 will be estimated as the number of evaluable patients still alive at 6 months divided by the total number of evaluable patients followed for at least 6 months. Ninety-five percent confidence intervals for the 'success' probability will be calculated according to the approach of Duffy and Santner. Progression is defined as a 25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.
Outcome measures
| Measure |
Phase I, Arm A
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=41 Participants
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
n=41 Participants
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Progression-free Survival
|
—
|
17.1 Proportion of Successes
Interval 7.7 to 32.6
|
—
|
9.7 Proportion of Successes
Interval 3.2 to 24.1
|
SECONDARY outcome
Timeframe: From start of study registration to death due to any cause or until last follow-up, up to 5 yearsThe overall survival distribution will be estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
Phase I, Arm A
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=46 Participants
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
n=7 Participants
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
n=44 Participants
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Overall Survival
|
—
|
6.55 months
Interval 4.24 to 11.6
|
6.74 months
Interval 2.63 to
Value not reached
|
3.93 months
Interval 2.96 to 5.63
|
SECONDARY outcome
Timeframe: Up to 5 yearsThe proportion of patients in each response category will be summarized and 90% confidence intervals calculated assuming that the incidence of response is binomially distributed.
Outcome measures
| Measure |
Phase I, Arm A
n=12 Participants
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=49 Participants
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
n=9 Participants
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
n=45 Participants
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
Progression
|
.5 proportion of patients
Interval 0.25 to 0.75
|
.24 proportion of patients
Interval 0.15 to 0.37
|
0 proportion of patients
Interval 0.0 to 0.0
|
.47 proportion of patients
Interval 0.34 to 0.6
|
|
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
Stable
|
.5 proportion of patients
Interval 0.25 to 0.75
|
.59 proportion of patients
Interval 0.46 to 0.71
|
.89 proportion of patients
Interval 0.57 to 0.99
|
.42 proportion of patients
Interval 0.3 to 0.56
|
|
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
Regression
|
0 proportion of patients
Interval 0.0 to 0.0
|
.06 proportion of patients
Interval 0.02 to 0.15
|
0 proportion of patients
Interval 0.0 to 0.0
|
.022 proportion of patients
Interval 0.001 to 0.1
|
|
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
Partial Response
|
0 proportion of patients
Interval 0.0 to 0.0
|
0.02 proportion of patients
Interval 0.001 to 0.09
|
0 proportion of patients
Interval 0.0 to 0.0
|
0 proportion of patients
Interval 0.0 to 0.0
|
|
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
Complete Response
|
0 proportion of patients
Interval 0.0 to 0.0
|
0 proportion of patients
Interval 0.0 to 0.0
|
0 proportion of patients
Interval 0.0 to 0.0
|
0 proportion of patients
Interval 0.0 to 0.0
|
|
Objective Response, as Determined by a Neurological Exam, MRI, and/or CT Measurement
Unknown/Not Evaluated
|
0 proportion of patients
Interval 0.0 to 0.0
|
.08 proportion of patients
Interval 0.03 to 0.18
|
.11 proportion of patients
Interval 0.01 to 0.43
|
.09 proportion of patients
Interval 0.03 to 0.19
|
SECONDARY outcome
Timeframe: Time from study registration to date of disease progression or last follow-up, assessed up to 5 yearsKaplan-Meier survival curves will be used to estimate progression-time distributions.
Outcome measures
| Measure |
Phase I, Arm A
Phase I, Arm A, Dose Escalation
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=46 Participants
Phase II, Arm B, Group I (patients not undergoing surgery)
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm C
n=9 Participants
Phase II, Arm C, Group II (patients undergoing surgery)
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase II, Arm D
n=44 Participants
Phase II, Arm D, Group III (patients who received prior anti-VEGF therapy)
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Progression-free Survival
|
—
|
2.71 months
Interval 2.2 to 3.98
|
4.34 months
Interval 2.63 to
value not reached
|
1.87 months
Interval 1.48 to 2.23
|
Adverse Events
Phase II, Arm C
Serious events: 3 serious events
Other events: 9 other events
Deaths: 0 deaths
Phase I, Arm A
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Phase II, Arm B
Serious events: 15 serious events
Other events: 48 other events
Deaths: 0 deaths
Phase II, Arm D
Serious events: 11 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase II, Arm C
n=9 participants at risk
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase I, Arm A
n=12 participants at risk
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=49 participants at risk
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm D
n=45 participants at risk
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Cardiac disorders
Myocardial ischemia
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Eye disorders
Vision blurred
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Colonic perforation
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Esophageal mucositis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Esophageal pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
General disorders
Chest pain
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
General disorders
Fatigue
|
0.00%
0/9
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
6.7%
3/45 • Number of events 3
|
|
General disorders
Fever
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
General disorders
Multi-organ failure
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Hepatobiliary disorders
Hepatobiliary disease
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 2
|
|
Infections and infestations
Abdominal infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Bone infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Infections and infestations
Catheter related infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Infections and infestations
Esophageal infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Gallbladder infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Infective myositis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Opportunistic infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Pneumonia
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
0.00%
0/45
|
|
Infections and infestations
Skin infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Infections and infestations
Wound infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Investigations
Cardiac troponin I increased
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Investigations
Creatinine increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
Investigations
INR increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
Investigations
Leukocyte count decreased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
0.00%
0/45
|
|
Investigations
Platelet count decreased
|
0.00%
0/9
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
6.7%
3/45 • Number of events 3
|
|
Investigations
Serum cholesterol increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
4.4%
2/45 • Number of events 2
|
|
Investigations
Weight loss
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
4.4%
2/45 • Number of events 2
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
4.4%
2/45 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
4.4%
2/45 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
0.00%
0/9
|
16.7%
2/12 • Number of events 2
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum triglycerides increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Nervous system disorders
Ataxia
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Nervous system disorders
Leukoencephalopathy
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
0.00%
0/45
|
|
Nervous system disorders
Mini mental status examination abnormal
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
0.00%
0/45
|
|
Nervous system disorders
Seizure
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Psychiatric disorders
Confusion
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
Vascular disorders
Hemorrhage
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
4.4%
2/45 • Number of events 2
|
|
Vascular disorders
Thrombosis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
Other adverse events
| Measure |
Phase II, Arm C
n=9 participants at risk
Patients receive sorafenib PO BID on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
conventional surgery: Undergo surgery
|
Phase I, Arm A
n=12 participants at risk
Patients receive sorafenib orally (PO) twice daily (BID) on days 1-28 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm B
n=49 participants at risk
Patients receive sorafenib and temsirolimus at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
Phase II, Arm D
n=45 participants at risk
Patients receive sorafenib and temsirolimus as in phase I at the MTD (25mg temsirolimus and 200mg sorafenib).
sorafenib tosylate: Given PO
temsirolimus: Given IV
|
|---|---|---|---|---|
|
General disorders
Localized edema
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
0.00%
0/45
|
|
General disorders
Pain
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
6.7%
3/45 • Number of events 3
|
|
Infections and infestations
Abdominal infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
0.00%
0/45
|
|
Infections and infestations
Bone infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
0.00%
0/45
|
|
Infections and infestations
Conjunctivitis infective
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Infections and infestations
Gingival infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Pneumonia
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Sinusitis
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Infections and infestations
Tooth infection
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 3
|
0.00%
0/45
|
|
Infections and infestations
Tracheitis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
22.2%
2/9 • Number of events 4
|
8.3%
1/12 • Number of events 1
|
24.5%
12/49 • Number of events 26
|
22.2%
10/45 • Number of events 15
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 3
|
13.3%
6/45 • Number of events 6
|
|
Investigations
Aspartate aminotransferase increased
|
22.2%
2/9 • Number of events 2
|
16.7%
2/12 • Number of events 7
|
24.5%
12/49 • Number of events 23
|
20.0%
9/45 • Number of events 15
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
4.4%
2/45 • Number of events 3
|
|
Investigations
CD4 lymphocytes decreased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 3
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Investigations
Creatine phosphokinase increased
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Investigations
Creatinine increased
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 7
|
6.7%
3/45 • Number of events 6
|
|
Investigations
INR increased
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
4.4%
2/45 • Number of events 4
|
|
Investigations
Laboratory test abnormal
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
22.2%
2/9 • Number of events 6
|
25.0%
3/12 • Number of events 6
|
14.3%
7/49 • Number of events 9
|
11.1%
5/45 • Number of events 5
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/9
|
0.00%
0/12
|
8.2%
4/49 • Number of events 6
|
17.8%
8/45 • Number of events 13
|
|
Investigations
Neutrophil count decreased
|
44.4%
4/9 • Number of events 14
|
33.3%
4/12 • Number of events 6
|
22.4%
11/49 • Number of events 21
|
11.1%
5/45 • Number of events 7
|
|
Investigations
Platelet count decreased
|
77.8%
7/9 • Number of events 49
|
58.3%
7/12 • Number of events 12
|
73.5%
36/49 • Number of events 70
|
80.0%
36/45 • Number of events 65
|
|
Investigations
Serum cholesterol increased
|
55.6%
5/9 • Number of events 15
|
58.3%
7/12 • Number of events 13
|
46.9%
23/49 • Number of events 55
|
55.6%
25/45 • Number of events 40
|
|
Investigations
Weight loss
|
22.2%
2/9 • Number of events 6
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
17.8%
8/45 • Number of events 10
|
|
Metabolism and nutrition disorders
Anorexia
|
55.6%
5/9 • Number of events 28
|
16.7%
2/12 • Number of events 2
|
42.9%
21/49 • Number of events 42
|
60.0%
27/45 • Number of events 38
|
|
Metabolism and nutrition disorders
Blood bicarbonate decreased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
22.2%
2/9 • Number of events 3
|
8.3%
1/12 • Number of events 1
|
32.7%
16/49 • Number of events 25
|
31.1%
14/45 • Number of events 25
|
|
Metabolism and nutrition disorders
Dehydration
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
20.4%
10/49 • Number of events 11
|
13.3%
6/45 • Number of events 9
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
6.1%
3/49 • Number of events 5
|
13.3%
6/45 • Number of events 7
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/9
|
16.7%
2/12 • Number of events 3
|
20.4%
10/49 • Number of events 14
|
24.4%
11/45 • Number of events 14
|
|
Gastrointestinal disorders
Nausea
|
11.1%
1/9 • Number of events 28
|
16.7%
2/12 • Number of events 7
|
40.8%
20/49 • Number of events 30
|
31.1%
14/45 • Number of events 19
|
|
Gastrointestinal disorders
Rectal pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9 • Number of events 3
|
16.7%
2/12 • Number of events 2
|
20.4%
10/49 • Number of events 12
|
15.6%
7/45 • Number of events 7
|
|
General disorders
Chest pain
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
0.00%
0/45
|
|
General disorders
Edema limbs
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
2.2%
1/45 • Number of events 3
|
|
General disorders
Fatigue
|
100.0%
9/9 • Number of events 49
|
91.7%
11/12 • Number of events 24
|
93.9%
46/49 • Number of events 135
|
86.7%
39/45 • Number of events 72
|
|
General disorders
Fever
|
0.00%
0/9
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
0.00%
0/45
|
|
General disorders
Flu-like symptoms
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
0.00%
0/45
|
|
General disorders
Gait abnormal
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 3
|
2.2%
1/45 • Number of events 1
|
|
Blood and lymphatic system disorders
Blood disorder
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
55.6%
5/9 • Number of events 18
|
75.0%
9/12 • Number of events 14
|
57.1%
28/49 • Number of events 82
|
48.9%
22/45 • Number of events 36
|
|
Ear and labyrinth disorders
External ear pain
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Endocrine disorders
Cushingoid
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Eye disorders
Cataract
|
11.1%
1/9 • Number of events 3
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Eye disorders
Diplopia
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Eye disorders
Dry eye syndrome
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Eye disorders
Eye pain
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Eye disorders
Vision blurred
|
11.1%
1/9 • Number of events 4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
2.2%
1/45 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Gastrointestinal disorders
Abdominal pain
|
44.4%
4/9 • Number of events 7
|
50.0%
6/12 • Number of events 9
|
22.4%
11/49 • Number of events 17
|
17.8%
8/45 • Number of events 10
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9 • Number of events 2
|
8.3%
1/12 • Number of events 2
|
22.4%
11/49 • Number of events 20
|
22.2%
10/45 • Number of events 15
|
|
Gastrointestinal disorders
Diarrhea
|
55.6%
5/9 • Number of events 39
|
41.7%
5/12 • Number of events 11
|
42.9%
21/49 • Number of events 46
|
33.3%
15/45 • Number of events 23
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 4
|
0.00%
0/45
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/9
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
6.7%
3/45 • Number of events 5
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Gastrointestinal disorders
Fecal incontinence
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
22.2%
2/9 • Number of events 2
|
16.7%
2/12 • Number of events 2
|
6.1%
3/49 • Number of events 4
|
15.6%
7/45 • Number of events 14
|
|
Metabolism and nutrition disorders
Serum calcium increased
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
6.7%
3/45 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
22.2%
2/9 • Number of events 2
|
25.0%
3/12 • Number of events 3
|
26.5%
13/49 • Number of events 24
|
33.3%
15/45 • Number of events 29
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
11.1%
1/9 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
10.2%
5/49 • Number of events 9
|
11.1%
5/45 • Number of events 6
|
|
Metabolism and nutrition disorders
Serum potassium increased
|
0.00%
0/9
|
8.3%
1/12 • Number of events 2
|
0.00%
0/49
|
6.7%
3/45 • Number of events 4
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
0.00%
0/9
|
0.00%
0/12
|
10.2%
5/49 • Number of events 8
|
13.3%
6/45 • Number of events 8
|
|
Metabolism and nutrition disorders
Serum sodium increased
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
6.7%
3/45 • Number of events 4
|
|
Metabolism and nutrition disorders
Serum triglycerides increased
|
44.4%
4/9 • Number of events 13
|
66.7%
8/12 • Number of events 12
|
42.9%
21/49 • Number of events 51
|
51.1%
23/45 • Number of events 40
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 4
|
2.2%
1/45 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
14.3%
7/49 • Number of events 11
|
6.7%
3/45 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
4.4%
2/45 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 4
|
4.4%
2/45 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
2.0%
1/49 • Number of events 3
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Upper extremity dysfunction
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/9
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
0.00%
0/45
|
|
Nervous system disorders
Cognitive disturbance
|
22.2%
2/9 • Number of events 3
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Nervous system disorders
Dizziness
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
10.2%
5/49 • Number of events 5
|
0.00%
0/45
|
|
Nervous system disorders
Dysgeusia
|
66.7%
6/9 • Number of events 32
|
33.3%
4/12 • Number of events 4
|
24.5%
12/49 • Number of events 27
|
31.1%
14/45 • Number of events 18
|
|
Nervous system disorders
Extrapyramidal disorder
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 3
|
0.00%
0/45
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 5
|
0.00%
0/12
|
14.3%
7/49 • Number of events 15
|
11.1%
5/45 • Number of events 7
|
|
Nervous system disorders
Ischemia cerebrovascular
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Nervous system disorders
Memory impairment
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
0.00%
0/49
|
11.1%
5/45 • Number of events 9
|
|
Nervous system disorders
Neurological disorder NOS
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 3
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
11.1%
1/9 • Number of events 2
|
8.3%
1/12 • Number of events 1
|
10.2%
5/49 • Number of events 18
|
6.7%
3/45 • Number of events 4
|
|
Nervous system disorders
Seizure
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
6.7%
3/45 • Number of events 3
|
|
Nervous system disorders
Speech disorder
|
22.2%
2/9 • Number of events 2
|
0.00%
0/12
|
0.00%
0/49
|
8.9%
4/45 • Number of events 4
|
|
Nervous system disorders
Tremor
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Nervous system disorders
Trigeminal nerve disorder
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 2
|
|
Psychiatric disorders
Confusion
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
4.4%
2/45 • Number of events 5
|
|
Psychiatric disorders
Depression
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
10.2%
5/49 • Number of events 5
|
2.2%
1/45 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/9
|
0.00%
0/12
|
16.3%
8/49 • Number of events 17
|
4.4%
2/45 • Number of events 3
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Renal and urinary disorders
Urinary frequency
|
0.00%
0/9
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
0.00%
0/45
|
|
Reproductive system and breast disorders
Vaginal dryness
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 3
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/9
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
4.4%
2/45 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
4.4%
2/45 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
4.4%
2/45 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal examination abnormal
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
2.2%
1/45 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
11.1%
1/9 • Number of events 2
|
0.00%
0/12
|
4.1%
2/49 • Number of events 3
|
8.9%
4/45 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.1%
1/9 • Number of events 1
|
16.7%
2/12 • Number of events 4
|
10.2%
5/49 • Number of events 10
|
4.4%
2/45 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
0.00%
0/9
|
25.0%
3/12 • Number of events 4
|
12.2%
6/49 • Number of events 13
|
13.3%
6/45 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 12
|
2.2%
1/45 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 3
|
8.9%
4/45 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/9
|
0.00%
0/12
|
6.1%
3/49 • Number of events 6
|
2.2%
1/45 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
77.8%
7/9 • Number of events 11
|
66.7%
8/12 • Number of events 11
|
55.1%
27/49 • Number of events 65
|
44.4%
20/45 • Number of events 34
|
|
Skin and subcutaneous tissue disorders
Scalp pain
|
0.00%
0/9
|
0.00%
0/12
|
0.00%
0/49
|
2.2%
1/45 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Sweating
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
11.1%
1/9 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
0.00%
0/45
|
|
Vascular disorders
Flushing
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Vascular disorders
Hematoma
|
0.00%
0/9
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Vascular disorders
Hemorrhage
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Vascular disorders
Hot flashes
|
0.00%
0/9
|
8.3%
1/12 • Number of events 3
|
6.1%
3/49 • Number of events 3
|
0.00%
0/45
|
|
Vascular disorders
Hypertension
|
44.4%
4/9 • Number of events 7
|
8.3%
1/12 • Number of events 1
|
46.9%
23/49 • Number of events 39
|
42.2%
19/45 • Number of events 32
|
|
Vascular disorders
Hypotension
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
|
Vascular disorders
Thrombosis
|
0.00%
0/9
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
0.00%
0/45
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60