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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00452413
Recruitment Status : Completed
First Posted : March 27, 2007
Results First Posted : May 13, 2021
Last Update Posted : May 13, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Malignant Solid Tumor Drug: enzastaurin Drug: erlotinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2007
Actual Primary Completion Date : July 2009
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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 Name: LY317615

Drug: erlotinib
Administered orally




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00452413


Locations
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United States, California
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, 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
United States, Kentucky
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.
Louisville, Kentucky, United States, 40207
United States, Maryland
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.
Baltimore, Maryland, United States, 21237
United States, Minnesota
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.
Minneapolis, Minnesota, United States, 55455
United States, Nebraska
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.
Omaha, Nebraska, United States, 68131
United States, Oregon
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.
Portland, Oregon, United States, 97213
United States, Tennessee
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.
Memphis, Tennessee, United States, 38104
United States, Texas
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.
Lubbock, Texas, United States, 79410
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00452413    
Other Study ID Numbers: 11183
H6Q-MC-S030 ( Other Identifier: Eli Lilly and Company )
First Posted: March 27, 2007    Key Record Dates
Results First Posted: May 13, 2021
Last Update Posted: May 13, 2021
Last Verified: April 2021
Additional relevant MeSH terms:
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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
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action