Study of Enzastaurin With 5-Fluorouracil/Leucovorin (5-FU/LV) Plus Bevacizumab as Maintenance Regimen Following First Line Therapy for Metastatic Colon Cancer

Study Overview
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Brief Summary
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This study will evaluate the addition of enzastaurin to 5-FU (5-fluorouracil)/LV (leucovorin) plus bevacizumab in the maintenance of best response obtained with 6 cycles of first-line therapy consisting of 5-FU/LV + oxaliplatin (FOLFOX) or 5-FU/LV + irinotecan (FOLFIRI), plus bevacizumab in patients with Metastatic Colorectal Cancer.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Enzastaurin With 5-FU/LV Plus Bevacizumab as Maintenance Regimen Following First Line Therapy for Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Enzastaurin
* Drug: Placebo
* Drug: Leucovorin (LV)
* Drug: 5-fluorouracil (5-FU)
* Drug: Bevacizumab (Bev)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of locally advanced or metastatic colorectal cancer (CRC) that is not curable. The histology types to be included are adenocarcinoma, mucinous adenocarcinoma, signet ring, and undifferentiated. Patients with neuroendocrine carcinomas will be excluded. Received 6 cycles (3 months [12 weeks]) of first-line therapy with FOLFOX or FOLFIRI, plus bevacizumab for metastatic CRC. Patients have received at least 5 cycles with bevacizumab. Patients who received 6 cycles of first-line therapy with FOLFOX or FOLFIRI, plus bevacizumab for recurrent CRC that has relapsed at least 12 months after completion of adjuvant therapy will also be included. All standard FOLFOX (FOLFIRI) regimens given on a biweekly schedule will be permitted; however, 21-day regimens will not be allowed. No more than 4 weeks may pass between the end of first-line therapy (that is, Day 14 of Cycle 6) and randomization. Documented evidence of tumor response of complete response (CR), partial response (PR), or stable disease (SD) by computed tomography (CT) scan or magnetic resonance imaging (MRI). Confirmation of response is not required. Exclusion Criteria: Are unable to swallow tablets. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Have known central nervous system metastases. Are receiving concurrent administration of any other antitumor therapy. Patients who have significant heart, liver, kidney, or psychiatric disease or have an active infection

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin + 5-FU/LV + Bev<br>5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with enzastaurin | Drug: Enzastaurin<br>* 1125 milligram (mg) loading dose, then 250 mg twice daily, oral up to 1 year (yr) or until progressive disease<br>* Other names: LY317615;Drug: Leucovorin (LV)<br>* 400 milligram per meter squared (mg/m^2) intravenously (IV), Day 1 of 14 day cycle (up to 1 yr or until progressive disease)<br>Drug: 5-fluorouracil (5-FU)<br>* 400 mg/m^2 bolus then 2400 mg/m^2 IV over 46 hours, Day 1 of 14 day cycle (up to 1 yr or until progressive disease)<br>Drug: Bevacizumab (Bev)<br>* 5 milligram per kilogram (mg/kg) IV, Day 1 of 14 day cycle (up to 1 yr or until progressive disease)<br>|
| Placebo Comparator: Placebo + 5-FU/LV + Bev<br>5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with placebo | Drug: Placebo<br>* oral, daily (up to 1 yr or until progressive disease)<br>Drug: Leucovorin (LV)<br>* 400 milligram per meter squared (mg/m^2) intravenously (IV), Day 1 of 14 day cycle (up to 1 yr or until progressive disease)<br>Drug: 5-fluorouracil (5-FU)<br>* 400 mg/m^2 bolus then 2400 mg/m^2 IV over 46 hours, Day 1 of 14 day cycle (up to 1 yr or until progressive disease)<br>Drug: Bevacizumab (Bev)<br>* 5 milligram per kilogram (mg/kg) IV, Day 1 of 14 day cycle (up to 1 yr or until progressive disease)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of Response Evaluation Criteria in Solid Tumor (RECIST) Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause. | Randomization to measured progressive disease or death up to 17.2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was the duration from enrollment to death due to any cause. For participants who are alive, OS is censored at the last contact. | Randomization up to 22.8 months | 
| Number of Participants With Adverse Events (AEs) | A summary of serious and all other non-serious AEs is located in the Reported Adverse Event module. | Randomization up to 17.2 months | 
| Overall Survival (OS) From Start of First Line Therapy | OS was the duration from first line therapy to death due to any cause. For participants who are alive, OS is censored at the last contact. | Start of first line therapy (approximately 3 months prior to randomization) to date of death from any cause up to 27 months post randomization | 
| PFS From Start of First Line Therapy | PFS was defined as the time from first line therapy to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of RECIST Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause. | Start of first line therapy to measured progressive disease or death up to 24 months |