The purpose of this study is to find a recommended dose of LY2940680 that can be safely given in combination with etoposide and carboplatin followed by LY2940680 alone in participants with extensive-disease small cell lung cancer. The study will also compare progression-free survival in participants who are administered etoposide, carboplatin and LY2940680 followed by LY2940680 alone versus etoposide, carboplatin, and placebo followed by placebo alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
26
Highlands Oncology Group
Fayetteville, Arkansas, United States
Northeast Georgia Cancer Care, LLC
Athens, Georgia, United States
Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)
MTD was defined as the highest tested dose that has \<33% probability of causing a dose-limiting toxicity(DLT). DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and fulfills any one of the following criterion using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE),version 4.0:Grade 3 non-hematological toxicity except nausea, vomiting, constipation, diarrhea, fatigue, or anorexia that is manageable with appropriate care,transient(i.e., ≤5 days) Grade 3 elevations of alanine aminotransferase(ALT) and/or aspartate aminotransferase(AST), without evidence of other hepatic injury, in the setting of preexisting hepatic metastasis, ≥Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia of any duration,CTCAE Grade 4 hematological toxicity of \>5 days duration and any febrile neutropenia. any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose-limiting.
Time frame: Baseline to Completion of the Phase 1b (Up To 12 Months)
Phase 2: Progression-Free Survival
Time frame: Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months)
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
Time frame: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
Time frame: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
Time frame: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
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Administered orally
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
New York Oncology Hematology Associate
Albany, New York, United States
Mount Sinai Medical Center
New York, New York, United States
Clinical Research Unit (ITOR) Greenville Hospital System
Greenville, South Carolina, United States
Accelerated Comm. Oncology Research Network (ACORN)
Memphis, Tennessee, United States
The West Clinic
Memphis, Tennessee, United States
US Oncology
The Woodlands, Texas, United States
Tyler Cancer Center
Tyler, Texas, United States
...and 4 more locations
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
Time frame: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Time frame: Baseline to Study Completion Up to 39 Months
Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells
The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated.
Time frame: Baseline, Cycle 2 Day 1, Cycle 7 Day 1
Phase 2: Overall Survival
Time frame: Randomization to Study Completion (Estimated as 38 Months)
Phase 2: Percent Change in Tumor Size (CTS)
Time frame: Randomization to End of Cycle 2 (Estimated as 24 Months)
Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)
Time frame: Randomization to Study Completion (Estimated as 38 Months)
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
Time frame: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
Time frame: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hours