Study of Enzastaurin Versus Placebo With Pemetrexed for Participants With Advanced or Metastatic Lung Cancer

A Phase 2 Double-Blind Randomized Study of Oral Enzastaurin HCl Versus Placebo Concurrently With Pemetrexed (Alimta®) as Second-Line Therapy in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

The purpose of this study is to determine if the combination of enzastaurin and pemetrexed can extend survival time without progression of disease for participants who have advanced or metastatic non-small cell lung cancer (NSCLC).

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: placebo; Drug: enzastaurin; Drug: pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38043
    • 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, 13009
    • 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.
  • Saint Herblain, France, 44805
    • 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.
  • Toulouse, France, 31059
    • 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.
  • Villejuif, France, 94805
    • 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
  • Gauting, Germany, 82131
    • 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.
  • Großhansdorf, Germany, D-22927
    • 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.
  • Köln, Germany, D-51109
    • 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
  • Aviano, Italy, 33081
    • 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.
  • Genova, Italy, 16132
    • 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.
  • Orbassano, Italy, 10043
    • 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.
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • 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.
• Portugal
  • Coimbra, Portugal, 3040-853
    • 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.
  • Lisbon, Portugal, 1099-035
    • 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.
  • Porto, Portugal, 4200-072
    • 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
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • 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.
  • California
    • Lancaster, California, United States, 93534
      • 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.
    • Los Angeles, California, United States, 90095
      • 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.
  • Florida
    • Tampa, Florida, United States, 33612
      • 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.
  • Kansas
    • Wichita, Kansas, United States, 67214
      • 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.
  • Maine
    • Scarborough, Maine, United States, 04074
      • 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.
  • Ohio
    • Dayton, Ohio, United States, 45429
      • 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.
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • 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
    • Fort Worth, Texas, United States, 76104
      • 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.
    • Richardson, Texas, United States, 75080
      • 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:

• Laboratory confirmed diagnosis of NSCLC with locally advanced or metastatic disease which cannot be cured.
• Participants must have disease which progressed after 1 prior systemic cytotoxic chemotherapy regimen for advanced disease.
• At least 1 measurable lesion.
• Must have stopped all previous systemic therapies for cancer for at least 2 weeks prior to enrollment.
• Must be able to follow study guidelines and be able to show up for appointments.

Exclusion Criteria:

• Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Previous treatment with enzastaurin or pemetrexed.
• Concurrent administration of any other antitumor therapy.
• Inability to swallow tablets.
• Pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pemetrexed + Enzastaurin	Drug: enzastaurin; 1125 milligrams (mg) loading dose then 500 mg, oral, daily Cycle 1 (28 days), subsequent cycles 21 days, until disease progression; Other Names: LY317615; Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenous (IV), day 8 Cycle 1 (28 days), day 1 subsequent cycles (21 days), until disease progression; Other Names: Alimta; LY231514
Placebo Comparator: Pemetrexed + Placebo	Drug: placebo; oral, daily; Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenous (IV), day 8 Cycle 1 (28 days), day 1 subsequent cycles (21 days), until disease progression; Other Names: Alimta; LY231514

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 date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date.	Baseline to measured progressive disease up to 9.92 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date the participant was last known to be alive.	Baseline to date of death from any cause up to 12.32 months
Time-to-Worsening (TW) in Lung Cancer Symptom Scale (LCSS) - Health Related Quality of Life (HRQoL) Subscale	LCSS is a participant rated lung cancer instrument which consisted of 6 disease related symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 quality of life (QoL) items (activity status, symptomatic distress, and overall QoL). TW in LCSS-HRQoL was measured from the date of enrollment to the first date of a 15 millimeters (mm) worsening in the 9th LCSS item on QoL. LCSS-HRQoL was measured on the 100-mm visual analogue scale (VAS) with the scores ranging from 0 (best response and very high HRQoL) to 100-mm (worse response and very low HRQoL). TW-HRQoL was censored at the date of the participant's last LCSS assessment for participant without a 15-mm increase on the 100-mm VAS.	Baseline to disease worsening up to 10.58 months
Duration of Disease Control (DDC)	DDC was defined as the time from randomization to the first documented observation of disease progression or death from any cause and was limited to the participants with a best tumor response of complete response (CR), partial response (PR), or stable disease (SD). Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. SD was defined as small changes that did not meet the above criteria. DDC was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death.	Baseline to measured progressive disease up to 9.92 months
Percentage of Participants With Complete Response or Partial Response (Tumor Response Rate)	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Participants with a best response of complete response (CR) or partial response (PR) were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants was calculated as the total number of participants affected divided by the number of participants analyzed then multiplied by 100.	Baseline to measured progressive disease up to 9.92 months
Tumor Biomarkers	Protein expression was measured using an Immunohistochemistry (IHC) assay from the tumor tissue samples. IHC histo-scores (H-scores) were determined separately for each of the 3 biomarkers: folate receptor alpha (FR alpha) in cytoplasm and apical membrane, thymidylate synthase (TS) in cytoplasm and nucleus, and thyroid transcription factor-1 (TTF1) in the nucleus. Tumor tissue samples were to be scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining. IHC H-score was calculated using the formula: 1 * (percentage of cells stained 1+) + 2 * (percentage of cells stained 2+) + 3 * (percentage of cells stained 3+), giving a minimum score of 0 to a maximum score of 300. The maximum score indicates the strongest expression.	Tumor samples collected at baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Died During the Study Treatment	Reported are the deaths due to study disease and adverse events (AEs) that occurred while on study treatment.	Baseline through study completion [up to 16 Cycles (21-day cycles, except Cycle 1 [28 days])]
Number of Participants Who Died During the 30 Days After Treatment Discontinuation	Reported are the deaths due to study disease and adverse events (AEs) that occurred during the 30 days after treatment discontinuation.	End of study treatment [16 Cycles (21-day cycles, except Cycle 1 [28 days])] through 30 days after treatment discontinuation

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST, Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: September 13, 2007
• First Submitted That Met QC Criteria: September 13, 2007
• First Posted (Estimate): September 17, 2007

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 9820; H6Q-MC-JCBT (Other Identifier: Eli Lilly and Company)