A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma

Study Overview
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Brief Summary
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The reason for this study is to see if the study drug LY3295668 erbumine is safe in participants with relapsed/refractory neuroblastoma.

Official Title
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A Phase 1 Study of Aurora Kinase A Inhibitor LY3295668 Erbumine as a Single Agent and in Combination in Patients With Relapsed/Refractory Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Drug: LY3295668 Erbumine
* Drug: Topotecan
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have relapsed/refractory neuroblastoma and have active disease in at least one site: bone, bone marrow or soft tissue. Participants must be able to submit an archival sample of tissue. Participants must be able to swallow capsules. Exclusion Criteria: Participants must not have had an allogeneic hematopoietic stem cell, bone marrow, or solid organ transplant. Participants must not have untreated tumor that has spread to the brain or spinal cord. Participants must not have a serious active disease other than neuroblastoma. Participants must not have a condition affecting absorption. Participants must not have had prior aurora kinase inhibitor exposure. Participants must not have a known allergy to the study treatment. Participants must not have symptomatic human immunodeficiency virus (HIV) infection or symptomatic activated/reactivated hepatitis A, B, or C.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 21 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3295668 Erbumine Escalation<br>LY3295668 Erbumine given orally. | Drug: LY3295668 Erbumine<br>* Administered orally.<br>|
| Experimental: LY3295668 Erbumine + Topotecan + Cyclophosphamide Escalation<br>LY3295668 Erbumine given orally and topotecan and cyclophosphamide given intravenously (IV). | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Topotecan<br>* Administered IV.<br>Drug: Cyclophosphamide<br>* Administered IV.<br>|
| Experimental: LY3295668 Erbumine Expansion<br>LY3295668 Erbumine given orally. | Drug: LY3295668 Erbumine<br>* Administered orally.<br>|
| Experimental: LY3295668 Erbumine + Topotecan + Cyclophosphamide Expansion<br>LY3295668 Erbumine given orally and topotecan and cyclophosphamide given IV. | Drug: LY3295668 Erbumine<br>* Administered orally.<br>Drug: Topotecan<br>* Administered IV.<br>Drug: Cyclophosphamide<br>* Administered IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) | Number of Participants with DLTs | Baseline through Cycle 2 (28 Day Cycle) | 
| Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) | ORR | Baseline through Measured Progressive Disease (Estimated up to 5 Years) | 
| Duration of Response (DoR) | DoR | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated up to 5 Years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3295668 | PK: AUC of LY3295668 | Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles) | 
| PK: AUC of LY3295668 in Combination with Topotecan and Cyclophosphamide | PK: AUC of LY3295668 in Combination with topotecan and cyclophosphamide | Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles) | 
| Best Overall Response (BOR): Percentage of Participants with CR, PR, Stable Disease (SD), or Progressive Disease (PD) | BOR | Baseline to Date of Objective Disease Progression (Estimated up to 5 Years) | 
| Progression-Free Survival (PFS) | PFS | Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 5 Years) | 
| Overall Survival (OS) | OS | Baseline to Date of Death from Any Cause (Estimated up to 6 Years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aurora kinase A, kinase, aurora A, aurora kinase inhibitor, aurora kinase A inhibitor, kinase inhibitor, AURKA, AurA, pediatric neuroblastoma, children