Trial Outcomes & Findings for Trial of Enzastaurin and Bevacizumab in Participants With Recurrent Malignant Gliomas (NCT NCT00586508)
NCT ID: NCT00586508
Last Updated: 2020-09-24
Results Overview
Data presented are the percentage of participants without progressive disease (PD) or death from any cause 6 months after registration. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
81 participants
Primary outcome timeframe
Registration to 6 months
Results posted on
2020-09-24
Participant Flow
The reasons for discontinuation listed in the participant flow are the reasons the participants discontinued treatment.
Participant milestones
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
Enzastaurin: 1125 milligrams (mg) loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on non-enzyme inducing antiepileptic drugs (NEIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 milligrams per kilogram (mg/kg), intravenously (IV), every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of progressive disease (PD), significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on enzyme inducing antiepileptic drugs (EIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Overall Study
STARTED
|
68
|
13
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
68
|
13
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
68
|
13
|
Reasons for withdrawal
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
Enzastaurin: 1125 milligrams (mg) loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on non-enzyme inducing antiepileptic drugs (NEIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 milligrams per kilogram (mg/kg), intravenously (IV), every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of progressive disease (PD), significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on enzyme inducing antiepileptic drugs (EIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Overall Study
Progressive disease
|
52
|
8
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Adverse Event
|
12
|
4
|
|
Overall Study
Withdrawal by Subject
|
4
|
0
|
Baseline Characteristics
Trial of Enzastaurin and Bevacizumab in Participants With Recurrent Malignant Gliomas
Baseline characteristics by cohort
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on NEIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on EIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50 years
FULL_RANGE 11.59 • n=5 Participants
|
44 years
FULL_RANGE 11.97 • n=7 Participants
|
49 years
FULL_RANGE 11.61 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
68 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
58 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
68 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Registration to 6 monthsPopulation: All enrolled participants who received at least 1 dose of study drug.
Data presented are the percentage of participants without progressive disease (PD) or death from any cause 6 months after registration. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Outcome measures
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on NEIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on EIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Progression-Free Survival at 6 Months (PFS-6)
|
31 percentage of participants
Interval 21.0 to 42.0
|
15 percentage of participants
Interval 2.0 to 39.0
|
PRIMARY outcome
Timeframe: Registration to PD, death or date of last contact up to 66.56 monthsPopulation: All enrolled participants who received at least 1 dose of study drug. The number of participants censored are 7 for Enzastaurin + Bevacizumab NEIAED) group and 0 for Enzastaurin + Bevacizumab (EIAED) group.
Defined as the time from registration to PD, death or date of last contact. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Participants who had no PD or death at the time of the data inclusion cutoff, time to PD was censored at their last tumor assessment prior to the cutoff date.
Outcome measures
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on NEIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on EIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Time to Progressive Disease (PD)
|
2.76 months
Interval 2.0 to 4.37
|
1.84 months
Interval 0.92 to 2.69
|
PRIMARY outcome
Timeframe: Registration to study completion up to 67.56 monthsPopulation: All enrolled participants who received at least 1 dose of study drug.
Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Outcome measures
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on NEIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on EIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) or Deaths (Safety)
SAEs
|
24 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events (AEs) or Deaths (Safety)
AEs
|
68 Participants
|
13 Participants
|
|
Number of Participants With Adverse Events (AEs) or Deaths (Safety)
Deaths
|
5 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Registration to date of objective PD or death up to 66.56 monthsPopulation: All enrolled participants who received at least 1 dose of study drug.
Overall response is confirmed complete response (CR) + partial response (PR). CR is complete disappearance of all measurable and evaluable disease, no new lesions, and no evidence of non-evaluable disease. PR is ≥50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions (or the 2 largest lesions), no progression of evaluable disease and no new lesions. ORR is calculated as (total number of participants with CR or PR from the start of registration until disease progression) / (the total number of participants treated)\*100.
Outcome measures
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on NEIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on EIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Overall Response Rate (ORR)
|
5.9 percentage of participants
Interval 1.6 to 14.4
|
0 percentage of participants
Zero participants had response; therefore 95% confidence interval was not calculated.
|
SECONDARY outcome
Timeframe: Baseline and every cycle (4-week cycles)Population: Data were not collected for any participant due to low samples.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Cycles 1-12 (4-week cycles)Population: All enrolled participants who received at least 1 dose of study drug and had HRQoL assessed at baseline and in the end of Cycles 1-12.
HRQoL was assessed with the Functional Assessment of Cancer Therapy - Brain (FACT-Br) version 4. The instrument consists of 50 items with a 5-point rating scale for each item, where 0 = "not at all" and 4 = "very much." Physical well-being, social/family well-being and functional well-being subscales consist of 7 items each with scores ranging from 0-28. The emotional well-being subscale consists of 6 items with a score ranging from 0-24. The brain cancer-specific subscale consists of 23 items with a score ranging from 0-92. Higher scores in each subscale represent better QoL. Changes from baseline in the 4 core subscales are presented.
Outcome measures
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on NEIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 Participants
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on EIAED for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 6
|
-2.9 units on a scale
Standard Deviation 6.18
|
-2.5 units on a scale
Standard Deviation 6.36
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 6
|
0.0 units on a scale
Standard Deviation 1.91
|
-1.0 units on a scale
Standard Deviation 2.83
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 1
|
1.4 units on a scale
Standard Deviation 3.27
|
2.5 units on a scale
Standard Deviation 4.04
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 2
|
1.2 units on a scale
Standard Deviation 3.15
|
2.0 units on a scale
Standard Deviation 4.36
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 3
|
2.3 units on a scale
Standard Deviation 4.60
|
-0.5 units on a scale
Standard Deviation 0.71
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 4
|
1.8 units on a scale
Standard Deviation 3.49
|
-3.0 units on a scale
Standard Deviation 2.83
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 5
|
1.0 units on a scale
Standard Deviation 1.87
|
0.5 units on a scale
Standard Deviation 0.71
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 6
|
-0.1 units on a scale
Standard Deviation 3.02
|
-1.0 units on a scale
Standard Deviation 1.41
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 7
|
-1.4 units on a scale
Standard Deviation 3.21
|
0.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 8
|
0.8 units on a scale
Standard Deviation 1.92
|
0.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 9
|
0.2 units on a scale
Standard Deviation 3.63
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 10
|
0.6 units on a scale
Standard Deviation 4.67
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 11
|
0.2 units on a scale
Standard Deviation 3.03
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Physical Well-Being Cycle 12
|
-0.5 units on a scale
Standard Deviation 2.08
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 1
|
-0.2 units on a scale
Standard Deviation 2.02
|
0.0 units on a scale
Standard Deviation 0.82
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 2
|
0.1 units on a scale
Standard Deviation 2.13
|
0.3 units on a scale
Standard Deviation 1.53
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 3
|
-0.1 units on a scale
Standard Deviation 2.47
|
0.5 units on a scale
Standard Deviation 0.71
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 4
|
-0.1 units on a scale
Standard Deviation 2.50
|
1.0 units on a scale
Standard Deviation 5.66
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 5
|
0.2 units on a scale
Standard Deviation 2.59
|
-1.5 units on a scale
Standard Deviation 2.12
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 7
|
0.0 units on a scale
Standard Deviation 2.55
|
-3.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 8
|
-1.2 units on a scale
Standard Deviation 1.30
|
-3.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 9
|
1.6 units on a scale
Standard Deviation 4.04
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 10
|
0.2 units on a scale
Standard Deviation 1.30
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 11
|
1.2 units on a scale
Standard Deviation 2.28
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Social/Family Well-Being Cycle 12
|
2.5 units on a scale
Standard Deviation 3.11
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 1
|
0.1 units on a scale
Standard Deviation 5.44
|
-1.8 units on a scale
Standard Deviation 2.50
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 2
|
-1.5 units on a scale
Standard Deviation 2.86
|
-4.0 units on a scale
Standard Deviation 2.65
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 3
|
-0.8 units on a scale
Standard Deviation 3.86
|
-4.5 units on a scale
Standard Deviation 0.71
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 4
|
-1.3 units on a scale
Standard Deviation 2.49
|
-3.5 units on a scale
Standard Deviation 0.71
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 5
|
-1.3 units on a scale
Standard Deviation 3.43
|
-1.0 units on a scale
Standard Deviation 4.24
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 6
|
-1.9 units on a scale
Standard Deviation 3.85
|
0.0 units on a scale
Standard Deviation 5.66
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 7
|
-4.2 units on a scale
Standard Deviation 3.56
|
-4.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 8
|
-2.4 units on a scale
Standard Deviation 2.51
|
-2.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 9
|
-1.8 units on a scale
Standard Deviation 1.79
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 10
|
-0.6 units on a scale
Standard Deviation 5.41
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 11
|
-2.0 units on a scale
Standard Deviation 2.45
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Emotional Well-Being Cycle 12
|
-1.3 units on a scale
Standard Deviation 3.59
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 1
|
0.7 units on a scale
Standard Deviation 6.57
|
3.0 units on a scale
Standard Deviation 4.76
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 2
|
0.3 units on a scale
Standard Deviation 5.58
|
1.0 units on a scale
Standard Deviation 4.36
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 3
|
0.1 units on a scale
Standard Deviation 5.41
|
1.0 units on a scale
Standard Deviation 1.41
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 4
|
-0.3 units on a scale
Standard Deviation 2.19
|
3.0 units on a scale
Standard Deviation 1.41
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 5
|
-1.4 units on a scale
Standard Deviation 3.64
|
0.5 units on a scale
Standard Deviation 2.12
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 7
|
-2.6 units on a scale
Standard Deviation 5.86
|
2.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 8
|
-3.8 units on a scale
Standard Deviation 4.71
|
3.0 units on a scale
Standard Deviation NA
1 participant was analyzed; therefore actual value was presented and standard deviation was not calculated.
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 9
|
-1.8 units on a scale
Standard Deviation 3.56
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 10
|
-3.6 units on a scale
Standard Deviation 5.22
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 11
|
-1.8 units on a scale
Standard Deviation 4.44
|
—
|
|
Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales
Functional Well-Being Cycle 12
|
-3.0 units on a scale
Standard Deviation 4.55
|
—
|
Adverse Events
Enzastaurin + Bevacizumab (NEIAED)
Serious events: 24 serious events
Other events: 68 other events
Deaths: 0 deaths
Enzastaurin + Bevacizumab (EIAED)
Serious events: 4 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 participants at risk
Enzastaurin: 1125 milligrams (mg) loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on non-enzyme inducing antiepileptic drugs (NEIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 milligrams per kilogram (mg/kg), intravenously (IV), every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of progressive disease (PD), significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 participants at risk
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on enzyme inducing antiepileptic drugs (EIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Cardiac disorders
Pericardial effusion
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
Colitis
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
Diarrhoea
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
Gastric perforation
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
Large intestine perforation
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
Nausea
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
Vomiting
|
4.4%
3/68 • Number of events 3
|
0.00%
0/13
|
|
General disorders
Death
|
2.9%
2/68 • Number of events 2
|
0.00%
0/13
|
|
General disorders
Disease progression
|
2.9%
2/68 • Number of events 2
|
0.00%
0/13
|
|
General disorders
Fatigue
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
General disorders
Medical device complication
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
General disorders
Sudden death
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
Infections and infestations
Gastric infection
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Investigations
Alanine aminotransferase increased
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Investigations
Aspartate aminotransferase increased
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Investigations
Blood glucose increased
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Investigations
Blood sodium increased
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Investigations
Lymphocyte count decreased
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Investigations
Platelet count decreased
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
Ataxia
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
Convulsion
|
10.3%
7/68 • Number of events 7
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
Haemorrhage intracranial
|
1.5%
1/68 • Number of events 1
|
15.4%
2/13 • Number of events 2
|
|
Nervous system disorders
Headache
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
Hydrocephalus
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
Peripheral motor neuropathy
|
2.9%
2/68 • Number of events 2
|
0.00%
0/13
|
|
Renal and urinary disorders
Renal failure
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
Vascular disorders
Hypertension
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Vascular disorders
Hypotension
|
1.5%
1/68 • Number of events 1
|
0.00%
0/13
|
|
Vascular disorders
Thrombosis
|
1.5%
1/68 • Number of events 1
|
23.1%
3/13 • Number of events 3
|
Other adverse events
| Measure |
Enzastaurin + Bevacizumab (NEIAED)
n=68 participants at risk
Enzastaurin: 1125 milligrams (mg) loading dose on Day 1, followed by 500 mg, orally, daily, for participants who are on non-enzyme inducing antiepileptic drugs (NEIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 milligrams per kilogram (mg/kg), intravenously (IV), every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of progressive disease (PD), significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
Enzastaurin + Bevacizumab (EIAED)
n=13 participants at risk
Enzastaurin: 1125 mg loading dose on Day 1, followed by 875 mg, orally, daily, for participants who are on enzyme inducing antiepileptic drugs (EIAED) for 4 weeks. Participants were evaluated after each cycle (4-week cycles).
Bevacizumab: 10 mg/kg, IV, every 2 weeks. Participants were evaluated after each cycle (4-week cycles).
Cycles repeated until there was evidence of PD, significant toxicity, withdrawal of consent, or other discontinuation criteria were met.
|
|---|---|---|
|
Cardiac disorders
Sinus tachycardia
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Endocrine disorders
Cushingoid
|
5.9%
4/68 • Number of events 4
|
0.00%
0/13
|
|
Eye disorders
Diplopia
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
Eye disorders
Vision blurred
|
4.4%
3/68 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
8.8%
6/68 • Number of events 6
|
23.1%
3/13 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhoea
|
20.6%
14/68 • Number of events 14
|
15.4%
2/13 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
2.9%
2/68 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
10.3%
7/68 • Number of events 7
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/68
|
15.4%
2/13 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
7.4%
5/68 • Number of events 5
|
0.00%
0/13
|
|
General disorders
Fatigue
|
36.8%
25/68 • Number of events 25
|
30.8%
4/13 • Number of events 4
|
|
General disorders
Medical device complication
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
General disorders
Oedema peripheral
|
7.4%
5/68 • Number of events 5
|
7.7%
1/13 • Number of events 1
|
|
Immune system disorders
Hypersensitivity
|
2.9%
2/68 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
|
Infections and infestations
Infection
|
5.9%
4/68 • Number of events 4
|
7.7%
1/13 • Number of events 1
|
|
Infections and infestations
Tooth infection
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
7.4%
5/68 • Number of events 5
|
0.00%
0/13
|
|
Investigations
Alanine aminotransferase increased
|
10.3%
7/68 • Number of events 7
|
7.7%
1/13 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
26.5%
18/68 • Number of events 18
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Blood albumin decreased
|
10.3%
7/68 • Number of events 7
|
7.7%
1/13 • Number of events 1
|
|
Investigations
Blood alkaline phosphatase increased
|
11.8%
8/68 • Number of events 8
|
7.7%
1/13 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
10.3%
7/68 • Number of events 7
|
7.7%
1/13 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
7.4%
5/68 • Number of events 5
|
0.00%
0/13
|
|
Investigations
Blood glucose increased
|
5.9%
4/68 • Number of events 4
|
0.00%
0/13
|
|
Investigations
Blood magnesium decreased
|
5.9%
4/68 • Number of events 4
|
0.00%
0/13
|
|
Investigations
Blood magnesium increased
|
33.8%
23/68 • Number of events 23
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Blood phosphorus decreased
|
26.5%
18/68 • Number of events 18
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Blood potassium increased
|
19.1%
13/68 • Number of events 13
|
30.8%
4/13 • Number of events 4
|
|
Investigations
Blood sodium decreased
|
22.1%
15/68 • Number of events 15
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Blood sodium increased
|
13.2%
9/68 • Number of events 9
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Blood uric acid increased
|
10.3%
7/68 • Number of events 7
|
0.00%
0/13
|
|
Investigations
Haemoglobin decreased
|
22.1%
15/68 • Number of events 15
|
23.1%
3/13 • Number of events 3
|
|
Investigations
Laboratory test abnormal
|
13.2%
9/68 • Number of events 9
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Lymphocyte count decreased
|
54.4%
37/68 • Number of events 37
|
7.7%
1/13 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
8.8%
6/68 • Number of events 6
|
15.4%
2/13 • Number of events 2
|
|
Investigations
Platelet count decreased
|
36.8%
25/68 • Number of events 25
|
23.1%
3/13 • Number of events 3
|
|
Investigations
Protein urine present
|
22.1%
15/68 • Number of events 15
|
7.7%
1/13 • Number of events 1
|
|
Investigations
Weight decreased
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
11.8%
8/68 • Number of events 8
|
15.4%
2/13 • Number of events 2
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.9%
4/68 • Number of events 4
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.4%
3/68 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
19.1%
13/68 • Number of events 16
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
4.4%
3/68 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
2.9%
2/68 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.9%
4/68 • Number of events 4
|
0.00%
0/13
|
|
Nervous system disorders
Cognitive disorder
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Convulsion
|
19.1%
13/68 • Number of events 13
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Headache
|
13.2%
9/68 • Number of events 9
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Memory impairment
|
5.9%
4/68 • Number of events 4
|
0.00%
0/13
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.9%
2/68 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
|
Nervous system disorders
Speech disorder
|
13.2%
9/68 • Number of events 9
|
7.7%
1/13 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
4.4%
3/68 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
1.5%
1/68 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Psychiatric disorders
Depression
|
7.4%
5/68 • Number of events 5
|
7.7%
1/13 • Number of events 1
|
|
Renal and urinary disorders
Chromaturia
|
16.2%
11/68 • Number of events 11
|
15.4%
2/13 • Number of events 2
|
|
Renal and urinary disorders
Urinary incontinence
|
7.4%
5/68 • Number of events 5
|
7.7%
1/13 • Number of events 1
|
|
Reproductive system and breast disorders
Menstruation irregular
|
9.1%
2/22 • Number of events 2
|
0.00%
0/4
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/68
|
7.7%
1/13 • Number of events 1
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.00%
0/22
|
25.0%
1/4 • Number of events 1
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/22
|
25.0%
1/4 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.4%
5/68 • Number of events 5
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
11.8%
8/68 • Number of events 8
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
13.2%
9/68 • Number of events 9
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
7.4%
5/68 • Number of events 5
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
14.7%
10/68 • Number of events 10
|
7.7%
1/13 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
11.8%
8/68 • Number of events 8
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
4.4%
3/68 • Number of events 3
|
15.4%
2/13 • Number of events 2
|
|
Vascular disorders
Hypertension
|
20.6%
14/68 • Number of events 14
|
7.7%
1/13 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60