A Study in Recurrent Glioblastoma (GB)

Study Overview
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Brief Summary
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The purpose of the study is to see whether treatment with LY2157299 on its own, LY2157299 plus lomustine therapy or lomustine plus placebo can help participants with brain cancer

Official Title
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A Phase 2 Study of LY2157299 Monohydrate Monotherapy or LY2157299 Monohydrate Plus Lomustine Therapy Compared to Lomustine Monotherapy in Patients With Recurrent Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: LY2157299 monohydrate
* Drug: Lomustine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmed diagnosis of relapsed intracranial GB Progressive Disease (PD) following standard chemoradiation Prior surgical resection allowed Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1 Adequate hematologic, hepatic and renal function Discontinued all prior cancer treatments for cancer & recovered from the acute effects of therapy Tumor specimen must be available for a central pathology review and prognostic and predictive biomarker evaluation Exclusion Criteria: Moderate or severe heart disease based on New York Heart Association (NYHA) criteria Prior nitrosurea therapy (including lomustine or Gliadel) Prior bevacizumab as 1st line treatment for GB (if treatment was concluded 12 months prior to enrollment, the patient may be eligible to participate in the trial) Current acute or chronic myelogenous leukemia Second primary malignancy that may affect the interpretation of results Serious concomitant systemic disorder

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2157299 monohydrate plus lomustine<br>300 mg/day LY2157299, given orally for 14 days, followed by 14 days of rest, equaling a 28-day cycle. First lomustine dose will be given as 100 mg/m2 on day 7 cycle 1. Remaining doses are based on the investigator's discretion and will be given orally once every 6 weeks in capsules to equal 100 to 130 mg/m2. | Drug: LY2157299 monohydrate<br>* Orally administered as tablets<br>* Other names: LY2157299;Drug: Lomustine<br>* Orally administered as capsules<br>|
| Experimental: LY2157299 monohydrate<br>300 mg/day LY2157299, given orally for 14 days, followed by 14 days of rest, equaling a 28-day cycle (unblinded) | Drug: LY2157299 monohydrate<br>* Orally administered as tablets<br>* Other names: LY2157299;|
| Active Comparator: lomustine plus placebo<br>First lomustine dose will be given as 100 mg/m2 on day 7 cycle 1. Remaining doses are based on the investigator's discretion and will be given orally once every 6 weeks in capsules to equal 100 to 130 mg/m2. LY2157299 monohydrate-matched placebo, given orally as tablets for 14 days, followed by 14 days of rest, equaling a 28-day cycle. | Drug: Lomustine<br>* Orally administered as capsules<br>Drug: Placebo<br>* Orally administered as tablets<br>* Other names: LY2157299 monohydrate-matched placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Date of randomization to date of death from any cause estimated up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population Pharmacokinetics (PK): median population clearance |  | Cycle 1, Day 1, 3, 14, 15 and 16 | 
| Progression free survival (PFS) |  | Randomization to the date of objective progression or death from any cause estimated up to 2 years | 
| Percentage of Participants with Tumor Response |  | Every 2 cycles to disease progression or participant starts a new anticancer therapy estimated up to 2 years | 
| Change from baseline in neurocognitive function |  | Baseline, cycle 1, cycle 2 then every 2 cycles to 30 day post discontinuation follow up estimated up to 2 years | 
| Population Pharmacokinetics (PK): absorption |  | Cycle 1, Day 1, 3, 14, 15 and 16 | 
| Population Pharmacokinetics (PK): volume of distribution |  | Cycle 1, Day 1, 3, 14, 15 and 16 | 
| Change from baseline in MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) score |  | Baseline, cycle 1, cycle 2 then every 2 cycles to 30 day post discontinuation follow up estimated up to 2 years |