Enzastaurin for Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Enzastaurin given daily to participants with colorectal cancer who have Stage 4 disease and have not received prior chemotherapy for advanced colorectal cancer

Official Title
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A Phase 2 Study of Oral Enzastaurin HCl in Patients With Metastatic Colorectal Cancer

Conditions
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Colonic Neoplasms

Intervention / Treatment
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* Drug: Enzastaurin HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with colorectal cancer that is advanced or metastatic (has spread to other parts of the body); able to visit the doctor's office every 28 days for at least 6 months; able to swallow tablets Exclusion Criteria: women cannot be pregnant or breastfeeding; no history of significant heart disease or any other significant medical problems as determined by the participant's physician

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin HCl<br> | Drug: Enzastaurin HCl<br>* 1200 milligrams (mg) loading dose orally, then 500 mg, orally, daily, up to six 28-day cycles.<br>* Other names: LY317615;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression Free Survival (PFS) at 6 Months | 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. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 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. | Baseline to measured progressive disease (PD) up to 24 months | 
| Overall Survival (OS) | 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. | Baseline to date of death from any cause up to 24 months | 
| Progression Free Survival (PFS) | 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. | Baseline to measured PD up to 9 months | 
| Duration of Stable Disease (SD) | 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. | Time from SD to measured PD up to 9 months | 
| Time to Treatment Response | 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. | Baseline to date of confirmed response up to 24 months | 
| Duration of Complete Response (CR) or Partial Response (PR) (Duration of Response) | 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. | Time from response to PD | 
| Number of Participants With Adverse Events (AEs) or Who Died | 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. | Baseline to study completion up to 24 months and 30-day post-study discontinuation | 
| Change From Baseline in QTc Interval | 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. | Baseline, Cycle 1 Day 1 and Cycle 2 Day 1 of 28-day cycles | 
| Pharmacokinetics-Minimum Observed Concentration (Cmin) of Total Analytes | Cmin of enzastaurin + LSN326020 (a metabolite of LY317615) after loading dose in Cycle 1 and at a steady state during Cycles 2 and 3. | Cycle 1 Day 2-predose, Cycle 2 Day 1-predose and Cycle 3 Day 1-predose of 28-day cycles | 
| Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each Cycle | CEA levels were measured to detect potentially rapid-growing tumors in participants who received enzastaurin. | Baseline and Cycles 1, 2, 3, 4, 5, 6 (28-day cycles) |