Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Etoposide

Carboplatin

Etoposide phosphate

Enzyme Inhibitors

Phase 1b Dose Escalation: Cycles 1-6 (21 day cycles) LY2940680 administered orally, once daily at escalating doses (100 milligrams \[mg\] up to 400 mg) in combination with etoposide (E) 100 milligram per square meter (mg/m\^2) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle and carboplatin (C) Area Under the Curve \[AUC\] 5 (mg•min/mL) administered by IV infusion on day 1 each cycle.

Phase 1b Maintenance: Cycles 7+ (21 day cycles) LY2940680 administered orally, once daily at the same dose as induction. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Induction: Cycles 1-6 (21 day cycles) Placebo administered orally once daily in combination with etoposide 100 mg/m2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle.

Maintenance: Cycles 7+ (21 day cycles) Placebo administered orally once daily. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Induction: Cycles 1-6 (21 day cycles) LY2940680 (dose to be determined in Phase 1b portion) administered orally once daily in combination with etoposide 100 mg/m\^2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle.

Maintenance: Cycles 7+ (21 day cycles). LY2940680 (dose to be determined in Phase 1 portion) administered orally once daily.

LY2940680

Placebo

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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.

A Study of LY2940680 in Small Cell Lung Cancer

A Phase 1b/2 Double-Blind Randomized Trial of the Hedgehog/SMO Antagonist LY2940680 in Combination With Carboplatin and Etoposide Followed by LY2940680 Versus Carboplatin and Etoposide Plus Placebo Followed by Placebo in Patients With Extensive-Stage Small Cell Lung Cancer

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This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

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.

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.

The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated.

Eli Lilly and Company

100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Phase 1b: 100 mg LY2940680 + C + E

200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Phase 1b: 200 mg LY2940680 + C + E

400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Phase 1b: 400 mg LY2940680 + C + E

100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Maintenance:

Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Phase 1b: 100 mg LY2940680 + C +E

200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Maintenance:

Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Maintenance:

Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

United Kingdom

Region of Enrollment

All participants who received at least one dose of study drug.

Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

Chief Medical Officer

Cohort 1:

100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Cohort 2:

200 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Cohort 3:

400 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Phase 1b

All participants who received at least one dose of study drug and were enrolled in Phase1b of the study.

Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)

400 mg LY2940680 administered orally QD cycles 1-6 (21 day cycle).

(AUC) 5 carboplatin (C) administered by IV infusion on day 1 each cycle.

100 mg/m\^2 etoposide (E) administered by IV infusion on days 1, 2, 3 of each cycle, followed by a single agent of LY2940680.

Phase 2: 400 mg LY2940680 + C+ E

Placebo administered orally QD for 6 cycles.

(AUC) 5 carboplatin administered by IV infusion on day 1 of each cycle.

100 mg/m\^2 etoposide administered by IV infusion on days 1, 2, 3 of each cycle.

Phase 2: Placebo + C + E

Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

Phase 2: Progression-Free Survival

LY2940680 Cycle 1, Day 1

LY2940680 Cycle 2, Day 1

LSN3185556 Cycle 1, Day 1

LSN3185556 Cycle 2, Day 1

100 mg LY2940680 administered orally once daily (QD) for 6 cycles.

100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

200 mg LY2940680 administered orally once daily (QD) for 6 cycles.

100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

400 mg LY2940680 administered orally once daily (QD) for 6 cycles.

100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Phase 1B: 400 mg LY2940680 + C + E

All participants who received at least one dose of study drug and were enrolled in Phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose

Total Carboplatin Cycle 1, Day 1

Total Carboplatin Cycle 2, Day 1

Etoposide Cycle 1, Day 1

Etoposide Cycle 2, Day 1

LY2940680 administered orally once daily (QD) for 6 cycles.

100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Phase 1b: LY2940680 + C + E

All participants who received at least one dose of study drug and were enrolled in Phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

C and E doses did not change for the 3 cohorts of LY (100,200 and 400 mg) so we only need to report one grouping.

Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose

Phase 1b: 100 mg LY2940680 + C+ E

Phase 1b: 200 mg LY2940680 + C+ E

Phase 1b: 400 mg LY2940680 + C+ E

All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose

Phase 1b: LY2940680 + C+ E

All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

C and E doses did not change for the 3 cohorts of LY (100,200 and 400 mg) so we only need to report one grouping.

Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose

100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

All participants who received at least one dose of drug.

Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

Phase 1b: 100 mg LY2940680

Phase 1b: 200 mg LY2940680

Phase 1b: 400 mg LY2940680

All participants who received at least one dose of drug and had samples available.

Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells

400 mg LY2940680 administered orally QD cycles 1-6 (21 day cycle)

(AUC) 5 carboplatin (C) administered by IV infusion on day 1 each cycle.

100 mg/m\^2 etoposide (E) administered by IV infusion on days 1, 2, 3 of each cycle, followed by a single agent of LY2940680.

Phase 2: Overall Survival

Phase 2: Percent Change in Tumor Size (CTS)

Induction: Cycles 1-6 (21 day cycles) Placebo administered orally once daily in combination with etoposide 100 mg/m\^2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle.

Maintenance: Cycles 7+ (21 day cycles) Placebo administered orally once daily. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Phase 2: LY2940680 + C+ E

Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)

LSN3185556 Cycle 1, Day 2

LSN3185556 Cycle 2, Day 2

Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose

Etoposide Cycle 2 ,Day 1

All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. C and E doses did not change for the 3 cohorts of LY (100,200 and 400 mg) so we only need to report one grouping.

Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose

100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve (AUC) 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Maintenance:

Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve (AUC) 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Maintenance:

Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

Area under the Curve (AUC) 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

Maintenance:

Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Spots Global Cancer Trial Database for A Study of LY2940680 in Small Cell Lung Cancer

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