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Enzastaurin for Patients With Metastatic Colorectal Cancer

Phase 2
Completed
Conditions
Colonic Neoplasms
Interventions
Registration Number
NCT00192114
Lead Sponsor
Eli Lilly and Company
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Enzastaurin HClEnzastaurin HCl-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Progression Free Survival (PFS) at 6 MonthsBaseline to 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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]Baseline to measured progressive disease (PD) up to 24 months

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.

Change From Baseline in QTc IntervalBaseline, Cycle 1 Day 1 and Cycle 2 Day 1 of 28-day cycles

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.

Progression Free Survival (PFS)Baseline to measured PD up to 9 months

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.

Number of Participants With Adverse Events (AEs) or Who DiedBaseline to study completion up to 24 months and 30-day post-study discontinuation

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.

Duration of Stable Disease (SD)Time from SD to measured PD up to 9 months

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.

Pharmacokinetics-Minimum Observed Concentration (Cmin) of Total AnalytesCycle 1 Day 2-predose, Cycle 2 Day 1-predose and Cycle 3 Day 1-predose of 28-day cycles

Cmin of enzastaurin + LSN326020 (a metabolite of LY317615) after loading dose in Cycle 1 and at a steady state during Cycles 2 and 3.

Overall Survival (OS)Baseline to date of death from any cause up to 24 months

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.

Time to Treatment ResponseBaseline to date of confirmed response up to 24 months

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.

Change From Baseline in Carcinoembryonic Antigen (CEA) Response at Each CycleBaseline and Cycles 1, 2, 3, 4, 5, 6 (28-day cycles)

CEA levels were measured to detect potentially rapid-growing tumors in participants who received enzastaurin.

Duration of Complete Response (CR) or Partial Response (PR) (Duration of Response)Time from response to PD

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.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

🇸🇪

Uppsala, Sweden

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇸🇪Uppsala, Sweden
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