CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma

Study Overview
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Brief Summary
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The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy (irinotecan and temozolamide) for Ewing's sarcoma that has come back or did not respond to treatment. This trial is part of the CAMPFIRE master protocol, which is a platform to speed development of new treatments for children and young adults with cancer. Your participation in this trial could last 11 months or longer, depending on how you and your tumor respond.

Official Title
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A Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib in Combination With Irinotecan and Temozolomide in Participants With Relapsed or Refractory Ewing's Sarcoma

Conditions
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Sarcoma, Ewing, Neoplasm Metastasis

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Irinotecan
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Ewing's sarcoma or Ewing's sarcoma-like tumor by institutional pathologist. The original pathological report is required. Repeat biopsy at progression is not required Refractory disease or confirmed radiological progression or recurrence following first or later line of treatment of Ewing's sarcoma or Ewing's sarcoma-like tumor -- Must have one measurable or evaluable lesion per RECIST 1.1 Adequate performance status based on age For participants less than (<)16 years of age, a Lansky score greater than or equal to (≥)50, or For participants ≥16 years of age, a Karnofsky score ≥50 Participants must have discontinued all previous treatments for cancer or investigational agents ≥7 days after the last dose and must have recovered from the acute effects Adequate hematologic and organ function less than or equal to (≤)14 days prior to Day 1 of Cycle 1: Absolute neutrophil count ≥1000/microliter (µL) Platelets ≥75,000/cubic millimeter (mm³) Hemoglobin ≥8 grams per deciLiter (g/Dl) (≥100 grams per Liter [g/L]) Total bilirubin ≤1.5 times (×) upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN Creatinine clearance or calculated glomerular filtration rate (GFR) ≥60 milliliters per minute per square meter (Ml/min/m²) or serum creatinine based on age/gender Female participants of childbearing potential must have a negative urine or serum pregnancy test Body weight ≥10 kilograms (kg) Must be able to swallow and/or have a gastric/nasogastric tube -- Participants in the European Union must be able to swallow intact capsules Stable or decreasing dose of steroids at least 7 days prior to enrollment Life expectancy of at least 8 weeks and able to complete at least 1 cycle of treatment Participants/caregivers are able and willing to make themselves available for the duration of the study and are willing to follow study procedures, including adherence to the pharmacokinetic (PK) sampling schedule Exclusion Criteria: Participants with severe and/or uncontrolled concurrent medical disease or psychiatric illness/social situation that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol Participants with an active fungal, bacterial, and/or known severe viral infection including, but not limited to, human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis. Participants who have had allogeneic bone marrow or solid organ transplant Surgery: Participants who have had, or are planning to have, the following invasive procedures: Major surgical procedure, laparoscopic procedure, or significant traumatic injury within 28 days prior to enrollment Surgical or other wounds must be adequately healed prior to enrollment Female participants who are pregnant or breastfeeding Have received any prior cyclin-dependent kinase (CDK) 4 and 6 inhibitor Progression during prior treatment with irinotecan and/or temozolomide Have a known intolerability or hypersensitivity to any of the study treatments or dacarbazine Diagnosed and/or treated additional malignancy within 3 years prior to enrollment

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 39 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: Abemaciclib + Irinotecan +Temozolomide<br>Abemaciclib given orally in combination with irinotecan given IV and temozolomide given orally. | Drug: Abemaciclib<br>* Orally<br>* Other names: LY2835219;Drug: Irinotecan<br>* IV<br>Drug: Temozolomide<br>* Orally<br>|
| Experimental: Irinotecan +Temozolomide<br>Irinotecan given IV and temozolomide orally. | Drug: Irinotecan<br>* IV<br>Drug: Temozolomide<br>* Orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS determined by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) | Baseline to objective progression or death due to any cause (estimated up to 11 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS | Baseline to date of death due to any cause (estimated up to 45 months) | 
| Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR | ORR | Baseline to measured progressive disease (estimated up to 11 months) | 
| Duration of Response (DoR) | DoR | Date of first evidence of CR or PR to date of disease recurrence, objective disease progression, or death due to any cause (estimated up to 11 months) | 
| Disease Control Rate (DCR) | DCR | Baseline to measured progressive disease (estimated up to 11 months) | 
| PFS | PFS determined by investigator assessment using RECIST 1.1 | Baseline to objective progression or death due to any cause (estimated up to 11 months) | 
| Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of Abemaciclib | PK: Cmin of Abemaciclib | Cycle 3, Day 1 (21 day cycles) | 
| Abemaciclib Product Acceptability | Participants evaluated abemaciclib acceptability (palatability and ease of administration) using a 5-category questionnaire. Participants were asked to select one of the following to describe the acceptability of abemaciclib: Very difficult, difficult, neither easy nor difficult, easy, or very easy. | Day 1 of Cycles 1 through 3 (21 day cycles) |