Trial Outcomes & Findings for Study of Enzastaurin Versus Placebo With Pemetrexed for Participants With Advanced or Metastatic Lung Cancer (NCT NCT00530621)
NCT ID: NCT00530621
Last Updated: 2020-07-01
Results Overview
PFS was defined as the time from date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
160 participants
Primary outcome timeframe
Baseline to measured progressive disease up to 9.92 months
Results posted on
2020-07-01
Participant Flow
Presented in the participant flow are the reasons participants discontinued from study treatment.
Participant milestones
| Measure |
Pemetrexed + Enzastaurin
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|
|
Overall Study
STARTED
|
80
|
80
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
79
|
80
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
80
|
80
|
Reasons for withdrawal
| Measure |
Pemetrexed + Enzastaurin
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|
|
Overall Study
Adverse Event
|
11
|
8
|
|
Overall Study
Physician Decision
|
2
|
4
|
|
Overall Study
Progressive Disease (PD)
|
47
|
40
|
|
Overall Study
Sponsor Decision
|
12
|
15
|
|
Overall Study
Subject Decision
|
4
|
7
|
|
Overall Study
Death
|
3
|
6
|
|
Overall Study
Not Treated Due to PD Prior to Dosing
|
1
|
0
|
Baseline Characteristics
Study of Enzastaurin Versus Placebo With Pemetrexed for Participants With Advanced or Metastatic Lung Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed + Enzastaurin
n=80 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total
n=160 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.2 years
STANDARD_DEVIATION 9.21 • n=5 Participants
|
61.6 years
STANDARD_DEVIATION 9.57 • n=7 Participants
|
61.4 years
STANDARD_DEVIATION 9.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
108 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
69 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
19 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Region of Enrollment
Portugal
|
5 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
21 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
South Korea
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Disease Stage at Study Entry
Stage IIIA
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Disease Stage at Study Entry
Stage IIIB
|
16 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Disease Stage at Study Entry
Stage IV
|
61 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to measured progressive disease up to 9.92 monthsPopulation: All randomized participants. Twenty five (25) participants in Pemetrexed + Enzastaurin group and twenty three (23) participants in Pemetrexed + Placebo group were censored for analysis.
PFS was defined as the time from date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=80 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Progression-Free Survival (PFS)
|
2.96 months
Interval 1.87 to 3.58
|
3.02 months
Interval 1.74 to 3.98
|
—
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause up to 12.32 monthsPopulation: All randomized participants. Fifty three (53) participants in Pemetrexed + Enzastaurin group and forty five (45) participants in Pemetrexed + Placebo group were censored for analysis.
OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date the participant was last known to be alive.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=80 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Overall Survival (OS)
|
9.63 months
Interval 8.18 to
Upper limit of 95% confidence interval was not estimable due to high censoring rate.
|
7.39 months
Interval 6.41 to
Upper limit of 95% confidence interval was not estimable due to high censoring rate.
|
—
|
SECONDARY outcome
Timeframe: Baseline to disease worsening up to 10.58 monthsPopulation: Randomized participants who had at least 1 baseline and 1 postbaseline LCSS assessment for HRQoL. Thirty (30) participants in Pemetrexed + Enzastaurin group and forty (40) participants in Pemetrexed + Placebo group were censored for the analysis.
LCSS is a participant rated lung cancer instrument which consisted of 6 disease related symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 quality of life (QoL) items (activity status, symptomatic distress, and overall QoL). TW in LCSS-HRQoL was measured from the date of enrollment to the first date of a 15 millimeters (mm) worsening in the 9th LCSS item on QoL. LCSS-HRQoL was measured on the 100-mm visual analogue scale (VAS) with the scores ranging from 0 (best response and very high HRQoL) to 100-mm (worse response and very low HRQoL). TW-HRQoL was censored at the date of the participant's last LCSS assessment for participant without a 15-mm increase on the 100-mm VAS.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=63 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=61 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Time-to-Worsening (TW) in Lung Cancer Symptom Scale (LCSS) - Health Related Quality of Life (HRQoL) Subscale
|
3.06 months
Interval 2.37 to 4.63
|
8.08 months
Interval 3.81 to
Upper limit of 95% confidence interval was not estimable due to high censoring rate.
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease up to 9.92 monthsPopulation: Randomized participants who received at least 1 dose of study drug and had a best tumor response of CR, PR, or SD. Fourteen (14) participants in Pemetrexed + Enzastaurin group and seventeen (17) participants in Pemetrexed + Placebo group were censored for analysis.
DDC was defined as the time from randomization to the first documented observation of disease progression or death from any cause and was limited to the participants with a best tumor response of complete response (CR), partial response (PR), or stable disease (SD). Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. SD was defined as small changes that did not meet the above criteria. DDC was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=38 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=38 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Duration of Disease Control (DDC)
|
5.32 months
Interval 3.58 to 7.13
|
6.31 months
Interval 4.4 to 6.93
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease up to 9.92 monthsPopulation: Randomized participants who received at least 1 dose of study drug and had responses evaluated for CR or PR.
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Participants with a best response of complete response (CR) or partial response (PR) were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants was calculated as the total number of participants affected divided by the number of participants analyzed then multiplied by 100.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=77 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=78 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Percentage of Participants With Complete Response or Partial Response (Tumor Response Rate)
|
3.9 percentage of participants
|
2.6 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Tumor samples collected at baselinePopulation: Randomized participants who had at least 1 biomarker expression value measured at baseline.
Protein expression was measured using an Immunohistochemistry (IHC) assay from the tumor tissue samples. IHC histo-scores (H-scores) were determined separately for each of the 3 biomarkers: folate receptor alpha (FR alpha) in cytoplasm and apical membrane, thymidylate synthase (TS) in cytoplasm and nucleus, and thyroid transcription factor-1 (TTF1) in the nucleus. Tumor tissue samples were to be scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining. IHC H-score was calculated using the formula: 1 \* (percentage of cells stained 1+) + 2 \* (percentage of cells stained 2+) + 3 \* (percentage of cells stained 3+), giving a minimum score of 0 to a maximum score of 300. The maximum score indicates the strongest expression.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=26 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=20 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
n=46 Participants
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Tumor Biomarkers
FR Alpha in Cytoplasm
|
55.96 H-scores
Standard Deviation 65.99
|
24.50 H-scores
Standard Deviation 51.04
|
41.98 H-scores
Standard Deviation 61.24
|
|
Tumor Biomarkers
TS in Nucleus
|
5.92 H-scores
Standard Deviation 12.55
|
8.00 H-scores
Standard Deviation 18.84
|
6.83 H-scores
Standard Deviation 15.44
|
|
Tumor Biomarkers
TTF-1 in Nucleus
|
47.88 H-scores
Standard Deviation 71.18
|
32.35 H-scores
Standard Deviation 72.58
|
41.13 H-scores
Standard Deviation 71.41
|
|
Tumor Biomarkers
FR Alpha in Apical Membrane
|
9.96 H-scores
Standard Deviation 24.70
|
18.25 H-scores
Standard Deviation 48.62
|
13.64 H-scores
Standard Deviation 37.03
|
|
Tumor Biomarkers
TS in Cytoplasm
|
16.38 H-scores
Standard Deviation 25.29
|
22.30 H-scores
Standard Deviation 34.83
|
18.96 H-scores
Standard Deviation 29.60
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through study completion [up to 16 Cycles (21-day cycles, except Cycle 1 [28 days])]Population: All randomized participants who received at least 1 dose of study drug.
Reported are the deaths due to study disease and adverse events (AEs) that occurred while on study treatment.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=79 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Number of Participants Who Died During the Study Treatment
Study Disease
|
2 Participants
|
3 Participants
|
—
|
|
Number of Participants Who Died During the Study Treatment
AEs
|
1 Participants
|
3 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: End of study treatment [16 Cycles (21-day cycles, except Cycle 1 [28 days])] through 30 days after treatment discontinuationPopulation: All randomized participants who received at least 1 dose of study drug.
Reported are the deaths due to study disease and adverse events (AEs) that occurred during the 30 days after treatment discontinuation.
Outcome measures
| Measure |
Pemetrexed + Enzastaurin
n=79 Participants
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 Participants
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Total (Pemetrexed + Enzastaurin and Pemetrexed + Placebo)
Enzastaurin (1125 mg loading dose of 9 tablets) or placebo (loading dose of 9 tablets) administered on Day 1 followed total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) or four placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin \[two 125-mg tablets administered orally 2 times a day\] or four placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|---|
|
Number of Participants Who Died During the 30 Days After Treatment Discontinuation
Study Disease
|
5 Participants
|
10 Participants
|
—
|
|
Number of Participants Who Died During the 30 Days After Treatment Discontinuation
AEs
|
2 Participants
|
0 Participants
|
—
|
Adverse Events
Pemetrexed + Enzastaurin
Serious events: 33 serious events
Other events: 73 other events
Deaths: 0 deaths
Pemetrexed + Placebo
Serious events: 30 serious events
Other events: 75 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed + Enzastaurin
n=79 participants at risk
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 participants at risk
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Anaemia of malignant disease
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Cardiac disorders
Atrial fibrillation
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Cardiac disorders
Cardiac failure acute
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Cardiac disorders
Palpitations
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Endocrine disorders
Adrenal insufficiency
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Anal ulcer
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Nausea
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Subileus
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
4/79 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Asthenia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Chest pain
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Disease progression
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Fatigue
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
General physical health deterioration
|
6.3%
5/79 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Pyrexia
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Hepatobiliary disorders
Cholangitis
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Febrile infection
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Listeriosis
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Lower respiratory tract infection
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Blood creatinine increased
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Malnutrition
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
1.3%
1/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Cerebrovascular accident
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Syncope
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Psychiatric disorders
Abnormal behaviour
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Renal and urinary disorders
Renal failure
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Renal and urinary disorders
Renal pain
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial fistula
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Mediastinal disorder
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Skin and subcutaneous tissue disorders
Panniculitis
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Vascular disorders
Hypotension
|
0.00%
0/79
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Vascular disorders
Thrombosis
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
Other adverse events
| Measure |
Pemetrexed + Enzastaurin
n=79 participants at risk
Enzastaurin 1125 milligrams (mg) loading dose \[total 9 tablets (three 125-mg tablets administered orally 3 times a day)\] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m\^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
Pemetrexed + Placebo
n=80 participants at risk
Placebo loading dose \[total 9 tablets (3 tablets administered orally 3 times a day)\] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m\^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle).
Pemetrexed 500 mg/m\^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle).
Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
29.1%
23/79 • Number of events 26
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
18.8%
15/80 • Number of events 22
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.1%
4/79 • Number of events 7
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 8
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
6.3%
5/79 • Number of events 9
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 7
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Neutropenia
|
19.0%
15/79 • Number of events 16
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
7.5%
6/80 • Number of events 9
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.9%
11/79 • Number of events 18
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 14
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Ear and labyrinth disorders
Vertigo
|
6.3%
5/79 • Number of events 7
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Eye disorders
Lacrimation increased
|
8.9%
7/79 • Number of events 7
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
7.5%
6/80 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.3%
1/79 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
10.0%
8/80 • Number of events 11
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.6%
6/79 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Constipation
|
24.1%
19/79 • Number of events 20
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
20.0%
16/80 • Number of events 19
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
21.5%
17/79 • Number of events 25
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
13.8%
11/80 • Number of events 13
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Dyspepsia
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Nausea
|
48.1%
38/79 • Number of events 52
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
25.0%
20/80 • Number of events 29
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Vomiting
|
24.1%
19/79 • Number of events 25
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
17.5%
14/80 • Number of events 18
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Asthenia
|
24.1%
19/79 • Number of events 22
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
21.2%
17/80 • Number of events 26
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Chest pain
|
11.4%
9/79 • Number of events 9
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
13.8%
11/80 • Number of events 11
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Fatigue
|
29.1%
23/79 • Number of events 29
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
30.0%
24/80 • Number of events 27
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
General physical health deterioration
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Mucosal inflammation
|
10.1%
8/79 • Number of events 13
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Oedema
|
5.1%
4/79 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Oedema peripheral
|
13.9%
11/79 • Number of events 13
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
10.0%
8/80 • Number of events 9
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Pyrexia
|
20.3%
16/79 • Number of events 28
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
17.5%
14/80 • Number of events 18
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Candidiasis
|
8.9%
7/79 • Number of events 7
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Alanine aminotransferase increased
|
7.6%
6/79 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Aspartate aminotransferase increased
|
5.1%
4/79 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 8
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Platelet count decreased
|
5.1%
4/79 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Weight decreased
|
11.4%
9/79 • Number of events 9
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
10.0%
8/80 • Number of events 8
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
35.4%
28/79 • Number of events 37
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
18.8%
15/80 • Number of events 16
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.5%
2/79 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
10.0%
8/80 • Number of events 8
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Dizziness
|
12.7%
10/79 • Number of events 13
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
6.2%
5/80 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Headache
|
8.9%
7/79 • Number of events 8
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Neuropathy peripheral
|
6.3%
5/79 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Psychiatric disorders
Anxiety
|
5.1%
4/79 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Psychiatric disorders
Confusional state
|
5.1%
4/79 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
0.00%
0/80
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Psychiatric disorders
Depression
|
5.1%
4/79 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Psychiatric disorders
Insomnia
|
8.9%
7/79 • Number of events 7
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
10.0%
8/80 • Number of events 13
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Renal and urinary disorders
Chromaturia
|
10.1%
8/79 • Number of events 8
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
1.2%
1/80 • Number of events 1
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.0%
15/79 • Number of events 16
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
20.0%
16/80 • Number of events 19
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.5%
13/79 • Number of events 13
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
18.8%
15/80 • Number of events 16
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.5%
2/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
5.0%
4/80 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
7.6%
6/79 • Number of events 6
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.3%
5/79 • Number of events 5
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
2.5%
2/80 • Number of events 2
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.1%
4/79 • Number of events 4
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
3.8%
3/80 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.8%
3/79 • Number of events 3
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
10.0%
8/80 • Number of events 10
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.5%
13/79 • Number of events 16
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
16.2%
13/80 • Number of events 15
Study-specific clinical outcomes due to progressive disease (PD) were not considered to be serious adverse events (SAEs) unless the investigator deemed it related to the use of the study drug.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60