A Study for Participants With Small-Cell Lung Cancer

Study Overview
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Brief Summary
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Part A: This study evaluates an experimental treatment in participants with extensive-disease in small-cell lung cancer. Part B: This study evaluates an experimental treatment in participants with extensive-disease in small-cell lung cancer.

Official Title
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A Phase 2 Study of LY2523355 in Patients With Extensive-Stage Small-Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: LY2523355
* Drug: Granulocyte colony-stimulating factor (G-CSF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histological or cytological evidence of extensive-disease small-cell lung cancer Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Have received at least 1 prior chemotherapy regimen with agents known to provide clinical benefit for small-cell lung cancer and be, in the opinion of the investigator, an appropriate candidate for experimental therapy Have discontinued all previous therapies for cancer, including chemotherapy, biologic therapy, hormone therapy, or radiotherapy. Participants must have recovered from the acute effects of therapy (except alopecia and fatigue) before study enrollment Part A: Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group scale Part B: Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group scale Exclusion Criteria: Have received treatment within 28 days of the first dose of LY2523355 with a drug that has not received regulatory approval for any indication Have a mixed histological diagnosis of small-cell lung cancer and non-small-cell lung cancer Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study Part A: Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and corticosteroid use has been discontinued for at least 2 weeks prior to the first dose of study drug. Screening of asymptomatic participants without history of CNS metastases is not required Part B: Have symptomatic, untreated, or uncontrolled CNS metastases or a history of CNS metastases. Participants who have received prophylactic radiation are not excluded. Screening of asymptomatic participants without history of CNS metastases is not required

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A LY2523355<br>8 milligrams per square meter (mg/m²) per dose based on participant's body surface area, administered intravenously as a 1-hour infusion on Days 1, 5, 9 of each 21-day cycle, until disease progression or unacceptable toxicity. | Drug: LY2523355<br>* Administered intravenously as a 1-hour infusion<br>|
| Experimental: Part B LY2523355<br>5 or 6 mg/m² per dose based on participant's body surface area, administered intravenously as a 1-hour infusion on Days 1, 2, 3 plus granulocyte colony-stimulating factor (G-CSF) support administered subcutaneously beginning on Day 4 of each 21-day cycle, until disease progression or unacceptable toxicity. | Drug: LY2523355<br>* Administered intravenously as a 1-hour infusion<br>Drug: Granulocyte colony-stimulating factor (G-CSF)<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants Achieving an Overall Response (Overall Response Rate) | The overall response is complete response (CR) + partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. The overall response rate is calculated as a total number of participants with CR or PR, then divided by the total number of participants treated, then multiplied by 100. | Date of enrollment to date of measured progressive disease up to 99.6 weeks | 
| Part B: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate) | Clinical benefit rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100. | Date of enrollment to date of measured progressive disease up to 18.1 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Progression-Free Survival | Progression-free survival (PFS) is defined as the time from the date of enrollment (first treatment dose) to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is a ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death or starting new anti-cancer therapy, PFS was censored at their last radiological tumor assessment. | Date of enrollment to date of measured progressive disease or date of death from any cause up to 99.6 weeks | 
| Part B: Progression-Free Survival | Progression-free survival (PFS) is defined as the time from the date of enrollment (first treatment dose) to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is a ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death or starting new anti-cancer therapy, PFS was censored at their last radiological tumor assessment. | Date of enrollment to date of measured progressive disease or date of death from any cause up to 18.1 weeks | 
| Part A: Percentage of Participants Achieving a Best Response (Clinical Benefit Rate) | Clinical benefit rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100. | Date of enrollment to date of measured progressive disease 99.6 weeks | 
| Part B: Percentage of Participants Achieving an Overall Response (Overall Response Rate) | The overall response is complete response (CR) + partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions. The overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated, then multiplied by 100. | Date of enrollment to date of measured progressive disease up to 18.1 weeks | 
| Part A: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 and Its Metabolite (LSN2546307) |  | Days 1,5 and 9 of Cycle 1 (21-day cycle) | 
| Part B: Pharmacokinetics - Maximum Observed Plasma Concentration (Cmax) of LY2523355 |  | Day 3 of Cycle 1 (21-day cycle) | 
| Part A: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)] | Due to the very limited pharmacokinetic sampling employed in Part A of the study, the AUC(0-∞) of LY2523355 could not be accurately calculated. | Days 1,5 and 9 of Cycle 1 (21-day cycle) | 
| Part B: Pharmacokinetics - Area Under the Plasma Concentration Versus Time Curve of LY2523355 From Time Zero to Infinity [AUC(0-∞)] |  | Day 3 of Cycle 1 (21-day cycle) | 
| Total Lung Cancer Symptom Scale (LCSS) and Average Symptom Burden Index (ASBI) | LCSS is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. The LCSS total score was defined as the mean of the 9 items of the scale, with scores range from 0 (for best outcome) to 100 (for worst outcome). ASBI was calculated as the mean of six symptom-specific questions from the LCSS, with scores range from 0 (for best outcome) to 100 (for worst outcome). | Baseline and follow-up up to 104 weeks after the first dose of study drug |