Trial Outcomes & Findings for Enzastaurin for Patients With Metastatic Colorectal Cancer (NCT NCT00192114)
NCT ID: NCT00192114
Last Updated: 2020-08-06
Results Overview
PFS defined as time from date of first dose of enzastaurin to first date of documented progressive disease (PD) or date of death (any cause), whichever occurred first. Using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) PD defined as ≥20% increase in sum of the longest diameter (LD) of target lesions, taking as reference smallest sum LD recorded since treatment started or appearance of ≥1 new lesions. Participants not known to have died as of data-inclusion cut-off date and who did not have PD, PFS was censored at date of last progression-free disease assessment prior to date of any post discontinuation anticancer therapy. Participants who took any subsequent systemic anticancer therapy prior to PD or death, PFS was censored at date of last progression-free disease assessment prior to the date of any post discontinuation anticancer therapy. PFS at 6 months = participants who were progression free and alive at 6 months divided by the number of treated participants x 100.
COMPLETED
PHASE2
28 participants
Baseline to 6 months
2020-08-06
Participant Flow
Participant flow reports those who discontinued from study drug.
Participant milestones
| Measure |
Enzastaurin HCl
1200 milligrams (mg) administered orally as a loading dose then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Overall Study
STARTED
|
28
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
28
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
24
|
Reasons for withdrawal
| Measure |
Enzastaurin HCl
1200 milligrams (mg) administered orally as a loading dose then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Overall Study
Objective Tumor Progression
|
19
|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Clinical Progression
|
2
|
|
Overall Study
Death
|
1
|
Baseline Characteristics
Enzastaurin for Patients With Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Age, Continuous
|
68.75 years
STANDARD_DEVIATION 8.80 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
15 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
0
|
24 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG)
1
|
4 Participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma colon
|
16 Participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma rectum
|
10 Participants
n=5 Participants
|
|
Pathological Diagnosis
Colorectal Cancer
|
1 Participants
n=5 Participants
|
|
Pathological Diagnosis
Other
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 monthsPopulation: All randomized participants who received at least 1 dose of study drug. Censored participants =5
PFS defined as time from date of first dose of enzastaurin to first date of documented progressive disease (PD) or date of death (any cause), whichever occurred first. Using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) PD defined as ≥20% increase in sum of the longest diameter (LD) of target lesions, taking as reference smallest sum LD recorded since treatment started or appearance of ≥1 new lesions. Participants not known to have died as of data-inclusion cut-off date and who did not have PD, PFS was censored at date of last progression-free disease assessment prior to date of any post discontinuation anticancer therapy. Participants who took any subsequent systemic anticancer therapy prior to PD or death, PFS was censored at date of last progression-free disease assessment prior to the date of any post discontinuation anticancer therapy. PFS at 6 months = participants who were progression free and alive at 6 months divided by the number of treated participants x 100.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Percentage of Participants With Progression Free Survival (PFS) at 6 Months
|
27.50 percentage of participants
Interval 12.53 to 44.82
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (PD) up to 24 monthsPopulation: All randomized participants who received at least 1 dose of study drug.
Objective response rate during treatment was defined as the number of participants with documented complete response (CR) or partial response (PR) divided by the total number of participants. CR and PR defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants with CR or PR (ORR) was the number of participants with documented CR or PR divided by the total number of treated participants x 100.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
|
0 percentage of participants
Not evaluable, no participants achieved CR or PR.
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause up to 24 monthsPopulation: All randomized participants who received at least 1 dose of study drug. Censored participants =23.
OS was defined as the time from the date of the first dose of enzastaurin to the date of death from any cause. Survival time was censored at the date of the last contact for participants who were still alive.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Overall Survival (OS)
|
23.38 months
Only 5 of 28 participants had events observed. Due to the high censoring rate and due to the pattern of censoring, the median is estimable but the 95% CI is undefined.
|
SECONDARY outcome
Timeframe: Baseline to measured PD up to 9 monthsPopulation: All randomized participants who received at least 1 dose of study drug. Censored participants =5.
PFS was defined as the time from the date of the first dose of enzastaurin to the first date of documented progressive disease (PD) or the date of death from any cause, whichever occurred first. Participants who were not known to have died as of the data-inclusion cut-off date, and who did not have PD, PFS was censored at the date of the last progression-free disease assessment date prior to the date of any post discontinuation anticancer therapy. Participants who took any subsequent systemic anticancer therapy prior to PD or death, PFS was censored at the date of the last progression-free disease assessment prior to the date of any post discontinuation anticancer therapy.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Progression Free Survival (PFS)
|
1.89 months
Interval 1.77 to 4.52
|
SECONDARY outcome
Timeframe: Time from SD to measured PD up to 9 monthsPopulation: Subset of all randomized participants who received at least 1 dose of study drug who achieved complete response (CR), partial response (PR) or SD. Censored participants =5.
Duration of SD measured from date of first dose of enzastaurin to date of documented progressive disease (PD) or date of death from any cause, whichever occurred first, using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). PD was defined as ≥20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD since treatment began or appearance of ≥1 new lesions. SD was defined as no improvement and not meeting the requirements of PD using smallest sum LD since treatment began as reference. Participants with SD (or better) who had not died at data-inclusion cut-off date without PD, or participants who took subsequent systemic anticancer therapy prior to PD or death, duration was censored at date of last progression-free disease assessment prior to the date of post discontinuation anticancer therapy.
Outcome measures
| Measure |
Enzastaurin HCl
n=12 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Duration of Stable Disease (SD)
|
6.13 months
Interval 3.64 to
Too few observations to determine upper level of 95% confidence interval.
|
SECONDARY outcome
Timeframe: Baseline to date of confirmed response up to 24 monthsPopulation: Zero participants were analyzed.
Time to treatment response was defined as date of first dose of study drug to the date of confirmed complete response (CR) or partial response (PR) using Response evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Time to treatment response was not evaluable, as there were no participants with CR or PR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from response to PDPopulation: Zero participants were analyzed.
The duration CR or PR was defined as the time from first objective status assessment of CR or PR to the first date of documented progressive disease (PD) or death from any cause. CR and PR were determined using Response evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Duration of response was not evaluable, as there were no participants with CR or PR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to study completion up to 24 months and 30-day post-study discontinuationPopulation: All randomized participants who received at least 1 dose of study drug.
Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs (regardless of causality). A summary of SAEs and other non-serious adverse events (AEs) regardless of causality is located in the Reported Adverse Events module. The number of participants who died included those who died due to an SAE (any cause) while on study and those who died due to progressive disease (PD) during the 30-day post-study discontinuation follow-up.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Number of Participants With Adverse Events (AEs) or Who Died
Serious AEs
|
4 Participants
|
|
Number of Participants With Adverse Events (AEs) or Who Died
AEs
|
22 Participants
|
|
Number of Participants With Adverse Events (AEs) or Who Died
Died due to PD during 30-day follow-up
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs) or Who Died
Died due to SAE while on study
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, Cycle 1 Day 1 and Cycle 2 Day 1 of 28-day cyclesPopulation: All randomized participants who received at least 1 dose of study drug.
QTc interval was a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A QTc interval adjusted using Bazette's correction (QTcB) was used in order to aid interpretation.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Change From Baseline in QTc Interval
Cycle 1 Day 1
|
2.07 milliseconds (msec)
Standard Deviation 16.21
|
|
Change From Baseline in QTc Interval
Cycle 2 Day 1
|
7.30 milliseconds (msec)
Standard Deviation 15.76
|
SECONDARY outcome
Timeframe: Cycle 1 Day 2-predose, Cycle 2 Day 1-predose and Cycle 3 Day 1-predose of 28-day cyclesPopulation: All randomized participants who received at least 1 dose of study drug.
Cmin of enzastaurin + LSN326020 (a metabolite of LY317615) after loading dose in Cycle 1 and at a steady state during Cycles 2 and 3.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Pharmacokinetics-Minimum Observed Concentration (Cmin) of Total Analytes
Cycle 1 Day 2
|
2180 nanomoles per liter (nmol/L)
Standard Deviation 1343
|
|
Pharmacokinetics-Minimum Observed Concentration (Cmin) of Total Analytes
Cycle 2 Day 1
|
1723 nanomoles per liter (nmol/L)
Standard Deviation 2042
|
|
Pharmacokinetics-Minimum Observed Concentration (Cmin) of Total Analytes
Cycle 3 Day 1
|
1374 nanomoles per liter (nmol/L)
Standard Deviation 936
|
SECONDARY outcome
Timeframe: Baseline and Cycles 1, 2, 3, 4, 5, 6 (28-day cycles)Population: All participants with both baseline and post baseline CEA measurements.
CEA levels were measured to detect potentially rapid-growing tumors in participants who received enzastaurin.
Outcome measures
| Measure |
Enzastaurin HCl
n=27 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle
Cycle 1
|
0.20 micrograms per liter (mcg/L)
Interval 0.0 to 0.7
|
|
Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle
Cycle 2
|
0.30 micrograms per liter (mcg/L)
Interval -1.6 to 36.6
|
|
Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle
Cycle 3
|
0.90 micrograms per liter (mcg/L)
Interval 0.1 to 2.3
|
|
Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle
Cycle 4
|
0.80 micrograms per liter (mcg/L)
Interval 0.4 to 3.3
|
|
Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle
Cycle 5
|
0.80 micrograms per liter (mcg/L)
Interval 0.35 to 3.4
|
|
Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle
Cycle 6
|
0.35 micrograms per liter (mcg/L)
Interval -0.25 to 14.85
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Cycle 2 and Cycle 3 (28-day cycles)Population: Participants with both baseline and post-baseline VEGF measurements.
VEGF levels were measured to detect potentially rapid-growing tumors in participants who received enzastaurin.
Outcome measures
| Measure |
Enzastaurin HCl
n=28 Participants
1200 milligrams (mg) administered orally as a loading dose, then 500 mg administered orally, once daily, for up to six 28-day cycles.
|
|---|---|
|
Change From Baseline in Vascular Endothelial Growth Factor (VEGF) to Cycle 2 and Cycle 3
Cycle 2
|
0.50 picograms per liter (pg/L)
Interval -4.4 to 34.3
|
|
Change From Baseline in Vascular Endothelial Growth Factor (VEGF) to Cycle 2 and Cycle 3
Cycle 3
|
-0.10 picograms per liter (pg/L)
Interval -2.4 to 3.15
|
Adverse Events
Enzastaurin HCl
Serious adverse events
| Measure |
Enzastaurin HCl
n=28 participants at risk
1200 milligrams (mg) of enzastaurin HCl administered orally as a loading dose then 500 mg, administered orally once daily up to six 28-day cycles.
|
|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Cardiac disorders
Cardiac failure
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Infection
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Pneumonia
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Dehydration
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Cerebral haemorrhage
|
3.6%
1/28 • Number of events 1
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
Other adverse events
| Measure |
Enzastaurin HCl
n=28 participants at risk
1200 milligrams (mg) of enzastaurin HCl administered orally as a loading dose then 500 mg, administered orally once daily up to six 28-day cycles.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
4/28 • Number of events 4
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Faeces discoloured
|
14.3%
4/28 • Number of events 4
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Nausea
|
21.4%
6/28 • Number of events 6
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Chills
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
General disorders
Fatigue
|
25.0%
7/28 • Number of events 7
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Nasopharyngitis
|
10.7%
3/28 • Number of events 3
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Infections and infestations
Urinary tract infection
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Blood creatinine increased
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Investigations
Blood urea
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Nervous system disorders
Dizziness
|
10.7%
3/28 • Number of events 3
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Renal and urinary disorders
Chromaturia
|
14.3%
4/28 • Number of events 4
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.9%
5/28 • Number of events 7
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.1%
2/28 • Number of events 2
Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60