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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Enzastaurin; Drug: Leucovorin (LV); Drug: 5-fluorouracil (5-FU); Drug: Bevacizumab (Bev); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • 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.
  • Krems, Austria, 3500
    • 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.
  • Salzburg, Austria, 5020
    • 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.
  • Vienna, Austria, 1100
    • 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.
• France
  • Brest, France, 29609
    • 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.
  • Caen, France, 14076
    • 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.
  • Clichy, France, 92118
    • 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.
  • Lille, France, 59020
    • 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.
  • Marseille, France, 13385
    • 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.
  • Paris, France, 75015
    • 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.
• Germany
  • Augsburg, Germany, D-86150
    • 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.
  • Frankfurt, Germany, D-60431
    • 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.
  • Heidelberg, Germany, D-69120
    • 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.
  • Luebeck, Germany, 23562
    • 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.
  • Muenchen, Germany, 81925
    • 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.
  • Munich, Germany, 81377
    • 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.
  • Weiden, Germany, 92637
    • 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.
• Italy
  • Bari, Italy, 70126
    • 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.
  • Bergamo, Italy, 24128
    • 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.
  • Firenze, Italy, 50139
    • 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.
  • Livorno, Italy, 57128
    • 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.
  • Milano, Italy, 20133
    • 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.
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • 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.
• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38138
      • 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.
  • Texas
    • Houston, Texas, United States, 77030
      • 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.
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Roche Pharma AG

Publications and helpful links

General Publications

• Wolff RA, Fuchs M, Di Bartolomeo M, Hossain AM, Stoffregen C, Nicol S, Heinemann V. A double-blind, randomized, placebo-controlled, phase 2 study of maintenance enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab after first-line therapy for metastatic colorectal cancer. Cancer. 2012 Sep 1;118(17):4132-8. doi: 10.1002/cncr.26692. Epub 2011 Dec 27.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: January 28, 2008
• First Submitted That Met QC Criteria: January 28, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin
• Other Study ID Numbers: 10534; H6Q-MC-S064 (Other Identifier: Eli Lilly and Company)