A Study of Prexasertib (LY2606368) in Participants With Extensive Stage Disease Small Cell Lung Cancer

Phase 2

Completed

Conditions: Small Cell Lung Cancer

Interventions: Drug: Prexasertib

Registration Number: NCT02735980

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to evaluate the safety and efficacy of prexasertib when given to participants with extensive stage disease small cell lung cancer (ED-SCLC). The study will evaluate how the body processes the drug and how the drug affects the body. The study will also evaluate the association between tumor response and the participant's perceived quality of life.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 133

Inclusion Criteria

Have ED-SCLC and have received a prior platinum-based regimen
Participants in Cohort 1 and in the addendum must have had an objective response to prior platinum-based therapy with subsequent progression ≥90 days after the last dose of platinum
Participants in Cohort 2 must have either not had an objective response to prior platinum based therapy or had progression <90 days after the last dose of platinum
Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group scale

Exclusion Criteria

Have received more than 2 prior therapies for ED-SCLC (including immunotherapy, targeted therapies, or chemotherapy)
Have symptomatic central nervous system (CNS) malignancy or metastasis. Asymptomatic participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids to treat CNS metastases
Have previously completed or withdrawn from this study or any other study investigating prexasertib or a checkpoint kinase I (CHK1) inhibitor or have shown hypersensitivity to any of the components of the prexasertib formulation
Have a serious cardiac condition

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prexasertib (Platinum Sensitive Disease)	Prexasertib	105 mg/m\^2 Intravenous (IV) prexasertib administered of every 14 days with extensive stage disease small cell lung cancer (ED-SCLC) who had platinum-sensitive disease (has prior platinum based therapy with subsequent progression greater or less than 90 days after last dose of platinum based therapy).
Prexasertib (Platinum Resistant Disease)	Prexasertib	105 mg/m\^2 IV prexasertib administered of every 14 days with extensive stage disease small cell lung cancer (ED-SCLC) who had resistant/refractory disease (did not have an objective response to platinum-based therapy or had progression greater than 90 days after the last dose of platinum).
Prexasertib Exploratory Addendum (Platinum Sensitive Disease)	Prexasertib	40 mg/m\^2 IV prexasertib Day 1, 2, and Day 3 of a 14 day cycle in participants with ED-SCLC platinum sensitive disease.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	Baseline to 10 months	ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics(PK): Maximum Concentration (Cmax) of Prexasertib Cohort 1 and Cohort 2	Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime	Pharmacokinetics(PK): Maximum Concentration of Prexasertib. The same dose was administered to Cohort 1 and Cohort 2 and were combined for analysis.
Pharmacokinetics(PK): Maximum Concentration of Prexasertib Cohort 3 (40 mg/m^2, Protocol Addenda)	Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime	Pharmacokinetics(PK): Maximum Concentration of Prexasertib
Duration of Response (DoR)	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause up to 9 months	DoR the time from the date of an objective response until Progressive Disease (PD): was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Disease Control Rate: Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD)	Baseline through Disease Progression or Death from Any Cause to 28 months	Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD.
Change From Baseline in Lung Cancer Symptom Scale Score (LCSS)	Baseline up to 9 months	LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).
Pharmacokinetics: Area Under the Concentration Curve of Prexasertib	Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime	Pharmacokinetics: Area Under the Concentration Curve of Prexasertib
Progression-Free Survival (PFS)	Baseline to Disease Progression or Death (up to 9 months)	PFS defined as the from randomization date to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Overall Survival (OS)	Baseline up to 28 months	OS defined as from randomization date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.
Change From Baseline on the Average Symptom Burden Index (ASBI)	Baseline up to 9 months	ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).

Trial Locations

Locations (17): Highlands Oncology Group
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Fayetteville, Arkansas, United States
Florida Cancer Specialists and Research Institute
🇺🇸
Saint Petersburg, Florida, United States
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
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.
🇬🇧
Sheffield, United Kingdom
Massachusetts General Hospital
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Danvers, Massachusetts, United States
Chattanooga Oncology Hematology Associates
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Chattanooga, Tennessee, United States
Sarah Cannon Cancer Center
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Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
"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."
🇫🇷
Montpellier, France
Florida Cancer Specialists
🇺🇸
Fort Myers, Florida, United States
Washington University Medical Center
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Saint Louis, Missouri, United States
Georgetown University Medical Center
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Washington, District of Columbia, United States
Dartmouth Hitchcock Medical Center
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Lebanon, New Hampshire, United States
Tennessee Oncology PLLC
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Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
The Center for Cancer and Blood Disorders
🇺🇸
Fort Worth, Texas, United States
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
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Seoul, Korea, Republic of