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

• ClinicalTrials.gov Identifier: NCT00530621
• Recruitment Status: Completed
• First Posted: September 17, 2007
• Results First Posted: July 1, 2020
• Last Update Posted: July 1, 2020
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: enzastaurin; Drug: placebo; Drug: pemetrexed	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2007
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: October 2008

Arms and Interventions

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 Name: 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: LY231514; Alimta
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: LY231514; Alimta

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Baseline to measured progressive disease up to 9.92 months ]
   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.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause up to 12.32 months ]
   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.
2. Time-to-Worsening (TW) in Lung Cancer Symptom Scale (LCSS) - Health Related Quality of Life (HRQoL) Subscale [ Time Frame: Baseline to disease worsening up to 10.58 months ]
   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.
3. Duration of Disease Control (DDC) [ Time Frame: Baseline to measured progressive disease up to 9.92 months ]
   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.
4. Percentage of Participants With Complete Response or Partial Response (Tumor Response Rate) [ Time Frame: Baseline to measured progressive disease up to 9.92 months ]
   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.
5. Tumor Biomarkers [ Time Frame: Tumor samples collected at baseline ]
   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.

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arkansas

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Fayetteville, Arkansas, United States, 72703

United States, California

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Lancaster, California, United States, 93534

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Los Angeles, California, United States, 90095

United States, Florida

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Tampa, Florida, United States, 33612

United States, Kansas

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Wichita, Kansas, United States, 67214

United States, Maine

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Scarborough, Maine, United States, 04074

United States, Ohio

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Dayton, Ohio, United States, 45429

United States, Tennessee

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Memphis, Tennessee, United States, 38120

United States, Texas

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Fort Worth, Texas, United States, 76104

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Richardson, Texas, United States, 75080

France

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Grenoble, France, 38043

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Marseille, France, 13009

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Saint Herblain, France, 44805

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Toulouse, France, 31059

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Villejuif, France, 94805

Germany

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Gauting, Germany, 82131

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Großhansdorf, Germany, D-22927

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Köln, Germany, D-51109

Italy

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Aviano, Italy, 33081

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Genova, Italy, 16132

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Orbassano, Italy, 10043

Korea, Republic of

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Seoul, Korea, Republic of, 135-710

Portugal

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Coimbra, Portugal, 3040-853

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Lisbon, Portugal, 1099-035

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Porto, Portugal, 4200-072

Sponsors and Collaborators

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

More Information

Additional Information:

Lilly Clinical Trial Registry 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00530621
• Other Study ID Numbers: 9820; H6Q-MC-JCBT ( Other Identifier: Eli Lilly and Company )
• First Posted: September 17, 2007
• Results First Posted: July 1, 2020
• Last Update Posted: July 1, 2020
• Last Verified: June 2020

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors