Trial Outcomes & Findings for Study of Enzastaurin Versus Placebo in the Treatment of Patients With Brain Metastases of Lung Cancer, After Whole Brain Radiation Therapy (NCT NCT00415363)
NCT ID: NCT00415363
Last Updated: 2020-11-05
Results Overview
Time to progression (TTP) of brain metastases is the time from randomization to first observation of brain metastases progression. Response Evaluation Criteria In Solid Tumors (RECIST; Version 1.0), using magnetic resonance imaging (MRI), until observation of objective progression, or clinically as the date of increased steroids dose (barring radiological confirmation), was used to assess progressive disease (PD) of brain metastases. TTP was right-censored with the date of last contact if the participant died without MRI-documented PD or symptomatic deterioration or was lost to follow-up or received post therapy (Radio, Systemic, Surgery) before documented PD of the brain metastases.
COMPLETED
PHASE2
109 participants
Baseline to measured progressive disease (up to 21.2 months)
2020-11-05
Participant Flow
Participant milestones
| Measure |
Enzastaurin
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Overall Study
STARTED
|
55
|
54
|
|
Overall Study
Safety Population
|
54
|
53
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
55
|
54
|
Reasons for withdrawal
| Measure |
Enzastaurin
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
|
Overall Study
Adverse Event
|
4
|
4
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Physician Decision
|
3
|
1
|
|
Overall Study
Death
|
16
|
12
|
|
Overall Study
Progressive disease
|
26
|
32
|
Baseline Characteristics
Study of Enzastaurin Versus Placebo in the Treatment of Patients With Brain Metastases of Lung Cancer, After Whole Brain Radiation Therapy
Baseline characteristics by cohort
| Measure |
Enzastaurin
n=55 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=54 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
Total
n=109 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.5 Years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
63.5 Years
STANDARD_DEVIATION 10.0 • n=7 Participants
|
63.0 Years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
26 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
Finland
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to measured progressive disease (up to 21.2 months)Population: Time to progressive disease (TTP) was analyzed on all randomized patients. Participants censored: Enzastaurin = 35 and Placebo = 32.
Time to progression (TTP) of brain metastases is the time from randomization to first observation of brain metastases progression. Response Evaluation Criteria In Solid Tumors (RECIST; Version 1.0), using magnetic resonance imaging (MRI), until observation of objective progression, or clinically as the date of increased steroids dose (barring radiological confirmation), was used to assess progressive disease (PD) of brain metastases. TTP was right-censored with the date of last contact if the participant died without MRI-documented PD or symptomatic deterioration or was lost to follow-up or received post therapy (Radio, Systemic, Surgery) before documented PD of the brain metastases.
Outcome measures
| Measure |
Enzastaurin
n=55 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=54 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Time to Progression of Brain Metastases
|
6.9 months
Interval 3.4 to 11.9
|
4.9 months
Interval 3.6 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 21.2 months)Population: TTOP was analyzed on randomized patients.
Time to objective progression (TTOP) of brain metastases is the time from randomization to the first observation of objective progression of brain metastases assessed by MRI. TTOP was right-censored with the date of the last objective progression-free disease assessment if the participant died or did not have objective PD as of the cut-off date. For participants receiving post-discontinuation therapy prior to PD of brain metastases, TTOP was censored at the last assessment before post-discontinuation therapy. Kaplan-Meier estimated the median survival times and confidence intervals.
Outcome measures
| Measure |
Enzastaurin
n=55 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=54 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Time to Objective Progression of Brain Metastases
|
5.0 months
Interval 3.1 to 8.4
|
3.7 months
Interval 3.4 to 8.2
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 14.4 months)Population: Progression-free survival was analyzed on all randomized participants.
Overall progression-free survival (PFS) is defined as the time from the date of study enrollment to the first date of progressive disease or death from any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at last contact date. For those who received subsequent systemic anticancer therapy (after discontinuation from study therapy) prior to objectively determined progression of brain metastases, PFS was censored at the start of radiotherapy for extracranial lesions or the date of starting chemotherapy.
Outcome measures
| Measure |
Enzastaurin
n=55 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=54 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Overall Progression-free Survival (Including Both Progression of Brain and Extracranial Tumor Lesion)
|
2.2 months
Interval 1.1 to 2.3
|
2.0 months
Interval 1.3 to 2.3
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause (up to 27.2 months)Population: OS was analyzed on all randomized patients.
Overall survival (OS) was defined as the time from randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS was censored at the last contact date.
Outcome measures
| Measure |
Enzastaurin
n=55 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=54 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Overall Survival
|
3.8 months
Interval 2.6 to 5.6
|
5.1 months
Interval 3.7 to 5.7
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 27.2 months)Population: Rate and 95% confidence intervals of overall response to treatment of extra-cranial tumor lesions were evaluated on all randomized participants who qualified for tumor response analysis by the following criteria: * Presence of measurable disease in at least one site other than brain * Treatment with at least one dose of study drug.
Overall Response (OR) was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). OR on extra-cranial tumors was assessed by response sequences. Complete response (CR) or partial response (PR), was confirmed by second assessment performed \>= 28 days after first response. Two CRs before progression required for best response of CR. Two PRs or better not qualifying for a CR, for best response of PR. * CR: Disappearance of all tumor lesions. * PR: 30% decrease from baseline in sum of the longest diameter of target lesions or complete disappearance of target lesions, without worsening of one or more nontarget lesions. In either case, no new lesions may have appeared. * Stable Disease (SD) is defined as disease that does not meet the criteria for CR, PR, or progressive disease (PD), and has been evaluated at least 1 time, at least 6 weeks after baseline assessment.
Outcome measures
| Measure |
Enzastaurin
n=41 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=44 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Complete Response
|
0 percentage of participants
Interval 0.0 to 8.6
|
0 percentage of participants
Interval 0.0 to 15.5
|
|
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Partial Response
|
0 percentage of participants
Interval 0.0 to 8.6
|
4.5 percentage of participants
Interval 0.6 to 15.5
|
|
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Stable Disease
|
12.2 percentage of participants
Interval 4.1 to 26.2
|
25.0 percentage of participants
Interval 13.2 to 40.3
|
|
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Progressive Disease
|
58.5 percentage of participants
Interval 42.1 to 73.7
|
47.7 percentage of participants
Interval 32.5 to 63.3
|
|
Overall Response (OR) to Treatment of Extra-cranial Tumor Lesions by Percentage of Participants
Unknown/Not Done
|
29.3 percentage of participants
Interval 16.1 to 45.5
|
22.7 percentage of participants
Interval 11.5 to 37.8
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 21.2 months)Population: Best overall tumor response (BOR) on brain metastases and 95% confidence intervals were evaluated on all randomized patients who qualified by the following criteria: * Presence of measurable disease in brain * Treatment with at least one dose of study drug
Best overall tumor response on brain metastases (BOR) according to RECIST V1.0 response criteria. For complete response (CR) or partial response (PR), BOR was to be confirmed. Response criteria were * CR: Disappearance of all tumor lesions. * PR: Either a) at least a 30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LDs or b) complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions. In either case, no new lesions may have appeared. * Stable Disease (SD) is defined as disease that does not meet the criteria for CR, PR, or progressive disease (PD), and has been evaluated at least 1 time, at least 6 weeks after baseline assessment.
Outcome measures
| Measure |
Enzastaurin
n=43 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=44 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Complete Response
|
0 percentage of participants
Interval 0.0 to 8.2
|
2.3 percentage of participants
Interval 0.1 to 12.0
|
|
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Partial Response
|
9.3 percentage of participants
Interval 2.6 to 22.1
|
4.5 percentage of participants
Interval 0.6 to 15.5
|
|
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Stable Disease
|
34.9 percentage of participants
Interval 21.0 to 50.9
|
50 percentage of participants
Interval 34.6 to 65.4
|
|
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Progressive Disease
|
14.0 percentage of participants
Interval 5.3 to 27.9
|
18.2 percentage of participants
Interval 8.2 to 32.7
|
|
Best Overall Tumor Response on Brain Metastases by Percentage of Participants
Unknown/Not Done
|
41.9 percentage of participants
Interval 27.0 to 57.9
|
25.0 percentage of participants
Interval 13.2 to 40.3
|
SECONDARY outcome
Timeframe: Baseline to 30 days after discontinuation (up to 17.6 months)Population: EORTC QLQ-C30 scores from all randomized patients who filled in at least baseline and one post baseline questionnaire were evaluated and summarized by means of descriptive statistics.
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Physical functioning was measured by items 1 to 5. Their sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better).
Outcome measures
| Measure |
Enzastaurin
n=42 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=43 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 3
|
-6.7 units on a scale
Interval -20.0 to 0.0
|
-8.3 units on a scale
Interval -20.0 to 0.0
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 6
|
-20.0 units on a scale
Interval -40.0 to 0.0
|
-13.3 units on a scale
Interval -30.0 to 6.7
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 9
|
-13.3 units on a scale
Interval -46.7 to -6.7
|
-13.3 units on a scale
Interval -30.0 to -6.7
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 12
|
-13.3 units on a scale
Interval -13.3 to 5.0
|
-26.7 units on a scale
Interval -46.7 to -6.7
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 15
|
6.7 units on a scale
Interval -6.7 to 20.0
|
-13.3 units on a scale
Interval -26.7 to 0.0
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 18
|
20.0 units on a scale
Interval 20.0 to 20.0
|
-30.0 units on a scale
Interval -40.0 to -6.7
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 21
|
0 units on a scale
Interval 0.0 to 0.0
|
13.3 units on a scale
Interval 0.0 to 13.3
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 24
|
20.0 units on a scale
Interval 20.0 to 20.0
|
13.3 units on a scale
Interval 13.3 to 13.3
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 27
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 30
|
0 units on a scale
Interval 0.0 to 0.0
|
-60.0 units on a scale
Interval -60.0 to -60.0
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
Week 33
|
0 units on a scale
Interval 0.0 to 0.0
|
-73.3 units on a scale
Interval -73.3 to -73.3
|
|
Health-related Quality of Life (HRQoL) EORTC QLQ-C30 Physical Functioning
30 days post last therapy
|
-13.3 units on a scale
Interval -40.0 to 0.0
|
-20.0 units on a scale
Interval -46.7 to -13.3
|
SECONDARY outcome
Timeframe: Baseline to 30 days after discontinuation (up to 17.6 months)Population: EORTC QLQ-C30 scores from all randomized patients who filled in at least baseline and one post baseline questionnaire were evaluated and summarized by means of descriptive statistics.
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100 (lower score is better).
Outcome measures
| Measure |
Enzastaurin
n=42 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=43 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 4
|
0 units on a scale
Interval 0.0 to 22.2
|
0 units on a scale
Interval 0.0 to 22.2
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 7
|
22.2 units on a scale
Interval 0.0 to 38.9
|
0 units on a scale
Interval -11.1 to 22.2
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 10
|
11.1 units on a scale
Interval -22.2 to 22.2
|
5.6 units on a scale
Interval -16.7 to 33.3
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 13
|
0 units on a scale
Interval -11.1 to 22.2
|
0 units on a scale
Interval -11.1 to 33.3
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 16
|
5.6 units on a scale
Interval -11.1 to 22.2
|
0 units on a scale
Interval -11.1 to 22.2
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 19
|
11.1 units on a scale
Interval 11.1 to 11.1
|
11.1 units on a scale
Interval -5.6 to 16.7
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 22
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval -11.1 to 11.1
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 25
|
22.2 units on a scale
Interval 22.2 to 22.2
|
-11.1 units on a scale
Interval -11.1 to -11.1
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 28
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 31
|
0 units on a scale
Interval 0.0 to 0.0
|
55.6 units on a scale
Interval 55.6 to 55.6
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
Week 34
|
0 units on a scale
Interval 0.0 to 0.0
|
77.8 units on a scale
Interval 77.8 to 77.8
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Fatigue
30 days post last therapy
|
0 units on a scale
Interval -11.1 to 11.1
|
22.2 units on a scale
Interval 0.0 to 55.6
|
SECONDARY outcome
Timeframe: Baseline to 30 days after discontinuation (up to 17.6 months)Population: EORTC QLQ-C30 scores from all randomized patients who filled in at least baseline and one post baseline questionnaire were evaluated and summarized by means of descriptive statistics. Median differences between treatment groups in change from baseline to every 4 weeks and the inter-quartile range are reported.
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100 (lower score is better).
Outcome measures
| Measure |
Enzastaurin
n=42 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=43 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 4
|
0 units on a scale
Interval -16.7 to 16.7
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 7
|
0 units on a scale
Interval -16.7 to 33.3
|
0 units on a scale
Interval 0.0 to 16.7
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 10
|
0 units on a scale
Interval -16.7 to 33.3
|
0 units on a scale
Interval 0.0 to 16.7
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 13
|
0 units on a scale
Interval 0.0 to 16.7
|
0 units on a scale
Interval -16.7 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 16
|
-16.7 units on a scale
Interval -33.3 to 0.0
|
0 units on a scale
Interval 0.0 to 33.3
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 19
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 22
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 25
|
33.3 units on a scale
Interval 33.3 to 33.3
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 28
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 31
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
Week 34
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Nausea/Vomiting
30 days post last therapy
|
0 units on a scale
Interval -16.7 to 33.3
|
0 units on a scale
Interval 0.0 to 16.7
|
SECONDARY outcome
Timeframe: Baseline to 30 days after discontinuation (up to 17.6 months)Population: EORTC QLQ-C30 scores from all randomized patients who filled in at least baseline and one post baseline questionnaire were evaluated and summarized by means of descriptive statistics. Median differences between treatment groups in change from baseline to every 4 weeks and the inter-quartile range are reported.
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100 (lower score is better).
Outcome measures
| Measure |
Enzastaurin
n=42 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=43 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 4
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 7
|
0 units on a scale
Interval 0.0 to 33.3
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 10
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 13
|
0 units on a scale
Interval 0.0 to 33.3
|
0 units on a scale
Interval -33.3 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 16
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 33.3
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 19
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval -16.7 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 22
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 25
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 28
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 31
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
Week 34
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - EORTC QLQ-C30 Diarrhea
30 days post last therapy
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 33.3
|
SECONDARY outcome
Timeframe: Baseline to 30 days after discontinuation (up to 17.6 months)Population: QLQ-BN20 scores were evaluated in all randomized patients who filled in at least baseline and one post baseline questionnaire. Scores were summarized by means of descriptive statistics. Median differences between treatment groups in change from baseline to every 4 weeks and the inter-quartile range are reported.
Health-related quality of life is measured using an EORTC quality of life questionnaire designed specifically for participants with brain tumors (BN-20). Questionnaires may be completed by the participant or with the assistance of the examiner at baseline prior to initiation of study therapy, and then approximately every 8 weeks while on study treatment (prior to discussing treatment response at each visit, whenever possible). All single questions are answered using a categorical scale (e.g., 1 = not at all; 2 = a little; 3 = quite a bit; 4 = very much) and linearly transformed to 0 to 100 scales with 1) higher scores for a functional scale representing higher levels of functioning, 2) higher scores for the global health status/quality of life representing higher levels of global health status/quality of life, 3) and higher scores for a symptom scale representing higher level of symptoms. For Headache lower score is better.
Outcome measures
| Measure |
Enzastaurin
n=31 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=33 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 4
|
0 units on a scale
Interval -33.3 to 0.0
|
0 units on a scale
Interval -33.3 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 7
|
0 units on a scale
Interval -33.3 to 33.3
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 10
|
-33.3 units on a scale
Interval -66.7 to 33.3
|
0 units on a scale
Interval -33.3 to 16.7
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 13
|
-16.7 units on a scale
Interval -33.3 to 16.7
|
0 units on a scale
Interval 0.0 to 16.7
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 16
|
-33.3 units on a scale
Interval -33.3 to -33.3
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 19
|
0 units on a scale
Interval 0.0 to 50.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 22
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 25
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 28
|
0 units on a scale
Interval 0.0 to 0.0
|
0 units on a scale
Interval 0.0 to 0.0
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 31
|
0 units on a scale
Interval 0.0 to 0.0
|
33.3 units on a scale
Interval 33.3 to 33.3
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
Week 34
|
0 units on a scale
Interval 0.0 to 0.0
|
66.7 units on a scale
Interval 66.7 to 66.7
|
|
HRQoL Questionnaire - QLQ-BN20 Headache
30 days post last therapy
|
0 units on a scale
Interval -33.3 to 0.0
|
0 units on a scale
Interval 0.0 to 33.3
|
SECONDARY outcome
Timeframe: every 6 weeks (up to 27.2 months)Population: Safety population of all participants who received at least one dose of study drug. All serious adverse events are reported. Other adverse events are reported with a threshold that they occurred in greater than 5% of patients.
A summary of serious adverse events (SAEs) and all other non-serious adverse events is located in the Reported Adverse Event Module.
Outcome measures
| Measure |
Enzastaurin
n=54 Participants
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=53 Participants
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Number of Participants With Adverse Events
Adverse Events
|
35 Participants
|
33 Participants
|
|
Number of Participants With Adverse Events
Serious Adverse Events
|
39 Participants
|
42 Participants
|
Adverse Events
Enzastaurin
Placebo
Serious adverse events
| Measure |
Enzastaurin
n=54 participants at risk
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=53 participants at risk
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Cardiac disorders
Atrial flutter
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/54
|
3.8%
2/53 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
3.7%
2/54 • Number of events 2
|
3.8%
2/53 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Gastrointestinal disorders
Nausea
|
5.6%
3/54 • Number of events 3
|
5.7%
3/53 • Number of events 3
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Gastrointestinal disorders
Pancreatitis
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
General disorders
Chest pain
|
3.7%
2/54 • Number of events 2
|
0.00%
0/53
|
|
General disorders
Death
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
General disorders
Fatigue
|
9.3%
5/54 • Number of events 5
|
5.7%
3/53 • Number of events 3
|
|
General disorders
General physical health deterioration
|
5.6%
3/54 • Number of events 3
|
0.00%
0/53
|
|
General disorders
Influenza like illness
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
3.7%
2/54 • Number of events 2
|
3.8%
2/53 • Number of events 3
|
|
Infections and infestations
Clostridium difficile colitis
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Diverticulitis
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Gastroenteritis
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Gastroenteritis norovirus
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Gastroenteritis viral
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Mycobacterium avium complex infection
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Infections and infestations
Neutropenic infection
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Pleural infection
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Pneumonia
|
11.1%
6/54 • Number of events 6
|
17.0%
9/53 • Number of events 9
|
|
Infections and infestations
Sepsis
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Sinusitis
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Injury, poisoning and procedural complications
Synovial rupture
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Investigations
Blood bilirubin increased
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.7%
2/54 • Number of events 2
|
1.9%
1/53 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.9%
1/54 • Number of events 1
|
1.9%
1/53 • Number of events 1
|
|
Nervous system disorders
Brain oedema
|
1.9%
1/54 • Number of events 1
|
1.9%
1/53 • Number of events 1
|
|
Nervous system disorders
Cerebral disorder
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Nervous system disorders
Depressed level of consciousness
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Nervous system disorders
Diplegia
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Nervous system disorders
Dizziness
|
1.9%
1/54 • Number of events 1
|
1.9%
1/53 • Number of events 1
|
|
Nervous system disorders
Epilepsy
|
1.9%
1/54 • Number of events 1
|
3.8%
2/53 • Number of events 7
|
|
Nervous system disorders
Headache
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Nervous system disorders
Intracranial pressure increased
|
1.9%
1/54 • Number of events 1
|
1.9%
1/53 • Number of events 1
|
|
Nervous system disorders
Multiple sclerosis relapse
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
1.9%
1/54 • Number of events 1
|
0.00%
0/53
|
|
Nervous system disorders
Somnolence
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/54
|
3.8%
2/53 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.7%
2/54 • Number of events 2
|
5.7%
3/53 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.7%
2/54 • Number of events 2
|
11.3%
6/53 • Number of events 6
|
|
Vascular disorders
Deep vein thrombosis
|
5.6%
3/54 • Number of events 3
|
3.8%
2/53 • Number of events 2
|
|
Vascular disorders
Hypotension
|
0.00%
0/54
|
1.9%
1/53 • Number of events 1
|
Other adverse events
| Measure |
Enzastaurin
n=54 participants at risk
Enzastaurin delivered as 1125 mg loading dose then 500 mg, oral, daily, until disease progression
|
Placebo
n=53 participants at risk
Placebo delivered as identical in appearance oral dose, daily.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.3%
5/54 • Number of events 5
|
7.5%
4/53 • Number of events 4
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
3/54 • Number of events 3
|
0.00%
0/53
|
|
Eye disorders
Vision blurred
|
1.9%
1/54 • Number of events 1
|
9.4%
5/53 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
4/54 • Number of events 5
|
1.9%
1/53 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
5.6%
3/54 • Number of events 3
|
5.7%
3/53 • Number of events 3
|
|
Gastrointestinal disorders
Dysphagia
|
1.9%
1/54 • Number of events 1
|
5.7%
3/53 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
35.2%
19/54 • Number of events 19
|
15.1%
8/53 • Number of events 9
|
|
Gastrointestinal disorders
Stomatitis
|
1.9%
1/54 • Number of events 1
|
5.7%
3/53 • Number of events 4
|
|
Gastrointestinal disorders
Vomiting
|
20.4%
11/54 • Number of events 11
|
11.3%
6/53 • Number of events 7
|
|
General disorders
Chest pain
|
1.9%
1/54 • Number of events 1
|
9.4%
5/53 • Number of events 5
|
|
General disorders
Fatigue
|
11.1%
6/54 • Number of events 6
|
11.3%
6/53 • Number of events 6
|
|
General disorders
Oedema peripheral
|
14.8%
8/54 • Number of events 9
|
5.7%
3/53 • Number of events 3
|
|
General disorders
Pyrexia
|
3.7%
2/54 • Number of events 2
|
7.5%
4/53 • Number of events 4
|
|
Infections and infestations
Oral candidiasis
|
3.7%
2/54 • Number of events 2
|
15.1%
8/53 • Number of events 8
|
|
Investigations
Urine colour abnormal
|
7.4%
4/54 • Number of events 4
|
0.00%
0/53
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.3%
5/54 • Number of events 5
|
3.8%
2/53 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.7%
2/54 • Number of events 2
|
5.7%
3/53 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.9%
1/54 • Number of events 1
|
7.5%
4/53 • Number of events 4
|
|
Nervous system disorders
Headache
|
3.7%
2/54 • Number of events 2
|
7.5%
4/53 • Number of events 5
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/54
|
7.5%
4/53 • Number of events 4
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/54
|
7.5%
4/53 • Number of events 4
|
|
Renal and urinary disorders
Chromaturia
|
11.1%
6/54 • Number of events 6
|
0.00%
0/53
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.4%
4/54 • Number of events 4
|
7.5%
4/53 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.0%
7/54 • Number of events 7
|
13.2%
7/53 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.9%
1/54 • Number of events 1
|
7.5%
4/53 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.6%
3/54 • Number of events 3
|
3.8%
2/53 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
1.9%
1/54 • Number of events 1
|
5.7%
3/53 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60