A Study of Enzastaurin and Erlotinib in Participants With Solid Tumors and Lung Cancer

April 20, 2021 updated by: Eli Lilly and Company

A Phase 1/2 Trial of Enzastaurin and Erlotinib in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer (NSCLC) After Prior Chemotherapy

Phase I: A study to see what doses of Enzastaurin and Erlotinib are best tolerated by participants with solid tumor cancer.

Phase II: A study to see how long participants with non-small cell lung cancer (NSCLC) treated with Enzastaurin and Erlotinib live.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • 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.
      • Palo Alto, California, United States, 94305
        • 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.
      • San Francisco, California, United States, 94143
        • 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.
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • 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.
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • 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.
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • 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.
    • Nebraska
      • Omaha, Nebraska, United States, 68131
        • 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.
    • Oregon
      • Portland, Oregon, United States, 97213
        • 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, 38104
        • 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
      • Lubbock, Texas, United States, 79410
        • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Phase 1: Any incurable solid malignancy, with no more than 3 prior systemic treatment regimens.

    Phase 2: Histologic diagnosis of advanced NSCLC, Stage IIIB with malignant pleural effusion or Stage IV per American Joint Committee on Cancer Staging Criteria for NSCLC. Participants must have failed 1 or 2 prior systemic treatment regimen(s).

  2. Performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale
  3. Prior chemotherapy must be completed at least 2 weeks prior to study enrollment, and the participant must have recovered from acute toxic effects (except alopecia) prior to enrollment.
  4. Prior radiotherapy is allowed to <25% of the bone marrow. Prior radiotherapy must be completed at least 2 weeks before study enrollment, and the participant must have recovered from acute toxic effects (except alopecia) prior to enrollment.
  5. Non-measurable or measurable disease as defined by Response Evaluation Criteria in Solid Tumors [RECIST, version (v) 1.0].

Exclusion Criteria:

Participants who

  1. Are unable to swallow tablets.
  2. Unable to discontinue use of carbamazepine, phenobarbital, and phenytoin.
  3. Have previously been treated with an epidermal growth factor receptor (EGFR) inhibitor, including erlotinib.
  4. Are receiving concurrent administration of any other antitumor therapy.
  5. Have received treatment within the last 30 days with a drug (not including study drug) that has not received regulatory approval for any indication at the time of study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Enzastaurin and erlotinib combination therapy

Enzastaurin:

  • Phase 1, Dose Level 1: 500 milligram (mg) oral loading dose Day 1, 250 mg oral, daily Day 2-28, 28-day cycle until disease progression
  • Phase 1, Dose Level 2: 1125 mg oral loading dose Day 1, 500 mg oral, daily until disease progression
  • Phase 2: Dose determined from Phase 1, oral, daily, 28-day cycles until disease progression

Erlotinib:

• 150 mg, oral, daily, 28-day cycles until disease progression
Drug: enzastaurin
Administered orally
Other Names:
  • LY317615
Drug: erlotinib
Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Phase 2 Dose for Enzastaurin Plus Erlotinib Combination Therapy (Assess the Tolerated Dose of the Combination Erlotinib and Enzastaurin)
Time Frame: Phase 1: Predose through end of Cycle 1 (28 days/cycle)
The recommended Phase 2 daily dose level was to be either 1 dose level below that in which 2 of 6 participants experienced dose-limiting toxicities (DLTs) in Phase 1 or the full doses of both enzastaurin and erlotinib (Phase 1, Dose Level 2) in the event that no more than 1 DLT occurred at the highest dose level (Dose Level 2). DLTs were defined as any of the following events during Phase 1, Cycle 1 that were considered by the investigator to be attributable to enzastaurin or the combination of enzastaurin with erlotinib: Grade 4 hematologic events; Grade 3 or 4 nonhematologic events except toxicities explained by a coexisting condition such as glucose disturbances in a diabetic or electrolyte imbalances from diarrhea or vomiting, and toxicities of nausea, vomiting, diarrhea, or skin rash that were tolerable with appropriate treatment.
Phase 1: Predose through end of Cycle 1 (28 days/cycle)
Phase 2: Progression-Free Survival (PFS) With the Enzastaurin Plus Erlotinib Combination Regimen
Time Frame: Phase 2: Baseline to measured PD (up to 20 months)
PFS was defined as the time from the date of study enrollment (baseline) to the first date of progressive disease (PD) (either objectively determined or clinical progression) or death from any cause. PD was defined by Response Evaluation Criteria in Solid Tumors [RECIST, version (v) 1.0] as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died as of the data cut-off date and who did not have PD, PFS was censored at the date of the last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from study treatment) prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post discontinuation anticancer therapy.
Phase 2: Baseline to measured PD (up to 20 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) (Safety and AE Profile for Enzastaurin/Erlotinib Combination)
Time Frame: Phase 1: First dose through 30 days post last dose (up to 14 Cycles, 28 days/cycle)
A TEAE is any untoward medical occurrence that either occurred or worsened any time after treatment baseline, which did not necessarily have a causal relationship with this treatment. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Phase 1: First dose through 30 days post last dose (up to 14 Cycles, 28 days/cycle)
Phase I: Pharmacokinetic (PK) Interactions Between Enzastaurin and Erlotinib: Apparent Oral Clearance of Erlotinib Under Steady State Conditions During Multiple Dosing (CLss/F)
Time Frame: Phase 1: Cycle 1, Day 22 [predose, 2 hours (h), 4 h, 6 h, 10 h postdose]
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL obtained after an oral dose (apparent oral CL) is influenced by the fraction of the dose absorbed (F). Drug CL is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent oral CL of erlotinib over 10 hours at steady state (ss) on Day 22 was calculated.
Phase 1: Cycle 1, Day 22 [predose, 2 hours (h), 4 h, 6 h, 10 h postdose]
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Time Frame: Phase 1: Cycle 1, Day 22 (predose, 2 h, 4 h, 6 h, 8 h postdose)
Maximum observed plasma concentration at steady state (Cmax,ss) of enzastaurin, its active metabolite (LSN326020) and total analyte were reported.
Phase 1: Cycle 1, Day 22 (predose, 2 h, 4 h, 6 h, 8 h postdose)
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Area Under the Plasma Concentration Time Curve at Steady State [AUC(Tau,ss)]
Time Frame: Phase 1, Cycle 1, Day 22 (predose, 2 h, 4 h, 6 h, and 8 h postdose)
Area under the plasma concentration time curve AUC(Tau,ss) of enzastaurin, its active metabolite (LSN326020) and total analyte were reported.
Phase 1, Cycle 1, Day 22 (predose, 2 h, 4 h, 6 h, and 8 h postdose)
Phase 2: Overall Survival (OS)
Time Frame: Phase 2: Baseline to date of death from any cause (up to 23 months)
OS was defined as the time from the date of study enrollment (baseline) to the date of death from any cause. For participants not known to have died as of the data cutoff date, OS was censored at the last contact date (last contact for participants in post discontinuation was equal to the last known alive date in mortality status).
Phase 2: Baseline to date of death from any cause (up to 23 months)
Phase 2: Duration of Response
Time Frame: Phase 2: Date of first response to date of PD (up to 18 months)
Duration of response: time from first objective assessment of complete response (CR) or partial response (PR) to first observation of PD. Using RECIST v1.0 criteria, CR was the disappearance of all target lesions; PR was either a ≥30% decrease in sum of LD of target lesions or a complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesion; PD was a ≥20% increase in sum of LD of target lesions, taking as references the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesion. For responding participants not known to have died and who did not have PD, duration of response was censored at date of the last visit with adequate assessment. For responding participants who received subsequent anticancer therapy (after discontinuation from study treatment) prior to PD, duration of response was censored at the date of last visit with adequate assessment prior to the initiation of post discontinuation anticancer therapy.
Phase 2: Date of first response to date of PD (up to 18 months)
Phase 2: Percentage of Participants With Tumor Response
Time Frame: Phase 2: Baseline to date of PD (up to 18 months)
Tumor response was defined using RECIST, v1.0 criteria. CR was the disappearance of all target lesions; PR was either a ≥30% decrease in sum of LD of target lesions or a complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesion. PD was a ≥20% increase in sum of LD of target lesions, taking as references the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesion. Stable Disease (SD) was defined as small changes that did not meet the above criteria. Percentage of participants with tumor response=[(number of participants with a CR, PR, SD, PD, and unknown response)/(total number of participants assessed)]*100.
Phase 2: Baseline to date of PD (up to 18 months)
Phase 2: Number of Participants Who Experienced TEAEs (Safety and AE Profile)
Time Frame: Phase 2: Baseline through 30 days post last dose (up to 24 Cycles, 28 days/cycle)
A TEAE is any untoward medical occurrence that either occurred or worsened any time after treatment baseline, which did not necessarily have a causal relationship with this treatment. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Phase 2: Baseline through 30 days post last dose (up to 24 Cycles, 28 days/cycle)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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 - 5PM Eastern time (UTC/GMT- 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (ACTUAL)

July 1, 2009

Study Completion (ACTUAL)

November 1, 2013

Study Registration Dates

First Submitted

March 23, 2007

First Submitted That Met QC Criteria

March 26, 2007

First Posted (ESTIMATE)

March 27, 2007

Study Record Updates

Last Update Posted (ACTUAL)

May 13, 2021

Last Update Submitted That Met QC Criteria

April 20, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11183 (Registry Identifier: DAIDS ES Registry Number)
  • H6Q-MC-S030 (OTHER: Eli Lilly and Company)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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