Trial of Enzastaurin and Bevacizumab in Participants With Recurrent Malignant Gliomas

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate both enzastaurin and bevacizumab in the treatment of recurrent malignant gliomas.

Official Title
-----------------
A Phase II Trial of Enzastaurin in Combination With Bevacizumab in Adults With Recurrent Malignant Gliomas

Conditions
-----------------
Recurrent Glioblastoma

Intervention / Treatment
-----------------
* Drug: enzastaurin
* Drug: bevacizumab
* Drug: Enzyme-inducing antiepileptic drugs (EIAED)
* Drug: Non-enzyme inducing antiepileptic drugs (NEIAED)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be at least 18 years old Participant must have been diagnosed with a recurrent brain tumor by magnetic resonance imaging (MRI) scan Participant must be willing to practice adequate contraception Participant must be able to swallow the enzastaurin tablets whole and receive bevacizumab intravenously Participant must agree to use the study drug only as instructed by your study doctor and staff. Exclusion Criteria: Women who are pregnant or breastfeeding Participants who have significant heart, liver, kidney, or psychiatric disease Participants who have an active infection Participants who have any recent bleeding in the brain Participants who are taking any anti-coagulation or anti-platelet medication [including aspirin, non-steroidal anti-inflammatories, Cyclooxygenase-2 (COX-2) inhibitors]

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin + Bevacizumab<br> | Drug: enzastaurin<br>* 1125 milligrams (mg) loading dose then 500 or 875 mg, orally, daily, 4-week cycles with participants evaluated after each cycle. The dose difference is for participants who are on enzyme-inducing antiepileptic drugs (EIAED) versus non-enzyme inducing antiepileptic drugs (NEIAED).<br>* Other names: LY317615;Drug: bevacizumab<br>* 10 milligrams per kilogram (mg/kg), intravenously (IV), every 2 weeks, participants are evaluated after each cycle (4-week cycles).<br>Drug: Enzyme-inducing antiepileptic drugs (EIAED)<br>* Administered orally<br>Drug: Non-enzyme inducing antiepileptic drugs (NEIAED)<br>* Administered orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival at 6 Months (PFS-6) | Data presented are the percentage of participants without progressive disease (PD) or death from any cause 6 months after registration. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). | Registration to 6 months | 
| Time to Progressive Disease (PD) | Defined as the time from registration to PD, death or date of last contact. PD was a 25% increase in the sum of products of all measurable lesions (or 2 largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Participants who had no PD or death at the time of the data inclusion cutoff, time to PD was censored at their last tumor assessment prior to the cutoff date. | Registration to PD, death or date of last contact up to 66.56 months | 
| Number of Participants With Adverse Events (AEs) or Deaths (Safety) | Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. | Registration to study completion up to 67.56 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response is confirmed complete response (CR) + partial response (PR). CR is complete disappearance of all measurable and evaluable disease, no new lesions, and no evidence of non-evaluable disease. PR is ≥50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions (or the 2 largest lesions), no progression of evaluable disease and no new lesions. ORR is calculated as (total number of participants with CR or PR from the start of registration until disease progression) / (the total number of participants treated)*100. | Registration to date of objective PD or death up to 66.56 months | 
| To Evaluate Tumor Markers and Genes |  | Baseline and every cycle (4-week cycles) | 
| Change From Baseline in Health-Related Quality of Life (HRQoL) Subscales | HRQoL was assessed with the Functional Assessment of Cancer Therapy - Brain (FACT-Br) version 4. The instrument consists of 50 items with a 5-point rating scale for each item, where 0 = not at all and 4 = very much. Physical well-being, social/family well-being and functional well-being subscales consist of 7 items each with scores ranging from 0-28. The emotional well-being subscale consists of 6 items with a score ranging from 0-24. The brain cancer-specific subscale consists of 23 items with a score ranging from 0-92. Higher scores in each subscale represent better QoL. Changes from baseline in the 4 core subscales are presented. | Baseline, Cycles 1-12 (4-week cycles) |