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Enzastaurin Before and Concomitant With Radiation, Followed by Enzastaurin in Participants With Newly Diagnosed Glioblastoma

Primary Purpose

Glioblastoma Multiforme

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Enzastaurin 500 milligram (mg) Once Daily (QD)

Enzastaurin 250 mg Twice Daily (BID)

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Present with newly diagnosed histologically proven supratentorial GBM.
Demonstration of an unmethylated MGMT-promotor
Participants must sign an informed consent document. Participants must be at least 18 years of age.
Estimated life expectancy of at least 12 weeks
Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of PKC-beta targets (for example, GSK3beta).
Disease evaluated by Gd-MRI (magnetic resonance imaging) within 72 hours postoperatively
Interval of greater than or equal to 2 and less than or equal to 4 weeks since surgery or biopsy
ECOG Performance Status of less than or equal to 2
Adequate organ function including the following:
adequate bone marrow reserve: white blood cell (WBC) count greater than or equal to 3.0 X 109/L, absolute neutrophil count (ANC) greater than or equal to 1.5 X 109/L, platelet count greater than or equal to 75.0 X 109/L, and hemoglobin greater than or equal to 10.0 g/dL (greater than or equal to 6.2 mmol/L).
Hepatic: bilirubin less than or equal to 1.5 times the upper limit of normal (X ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) less than or equal to 2.5 X ULN, or less than or equal to 5 X ULN with liver metastases
Renal: serum creatinine less than or equal to 1.5 X ULN
Blood clotting: prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits
Participants must discontinue use of enzyme-inducing antiepileptic drugs (EIAEDs) greater than or equal to 14 days prior to study enrollment. The investigator may prescribe non-EIAEDs. Participants who must begin EIAED therapy while on study will be allowed to remain on study.
Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG); no history of stroke

Exclusion Criteria:

Have a prior malignancy (other than glioblastoma, or adequately treated carcinoma in situ of the cervix, or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
Unable to undergo Gd MRI
Prior chemotherapy within the last 5 years
Prior chemotherapy for a brain tumor
Prior radiotherapy of the head
Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin
History of coagulation disorder associated with bleeding, or recurrent thrombotic events
Are receiving concurrent administration of anticoagulant therapy
Placement of Gliadel® wafer at surgery
Have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) - participants who are pregnant, anticipate becoming pregnant within 6 months after study participation, or are currently breast-feeding
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Enzastaurin Once Daily (QD)

Enzastaurin Twice Daily (BID)

Arm Description

Enzastaurin given orally (PO) once daily (QD). 1125 mg loading dose D(-)7 then 500 mg PO,QD with concomitant radiotherapy.

Enzastaurin 1125 mg loading dose D(-)7 then 250 mg twice daily (BID) PO, with concomitant radiotherapy.

Outcomes

Primary Outcome Measures

Percentage of Participants With Progression Free Survival at 6 Months (PFS-6)

PFS-6 is defined as the percentage of participants with PFS at 6 months from the date of diagnosis to the first date of objectively determined progressive disease (based on radiological assessment) or death from any cause. It is assumed that PFS follows an exponential distribution.Estimation using Kaplan-Meier technique.

Secondary Outcome Measures

Percentage of Participants With Overall Survival at 1 and 2 Years After Surgery

Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date. OS rate at 1 year (respectively 2 years) is determined using the OS times.

Response Rate

Response rate is calculated as the number of participants with best response: complete response(CR: disappearance of all enhancing tumor on consecutive CT or magnetic resonance imaging (MRI) scans at least 1 month apart, off steroids, and neurologically stable or improved ) or partial response (PR:-50% reduction in size of enhancing tumor on consecutive CT or MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved), divided by the number of participants treated, multiplied by 100. CR and PR were assessed according to the criteria defined by MacDonald et al. 1990. A CR or PR must be confirmed by a second assessment, performed ≥28 days after the first evidence of response.

Change in Neurologic Status as Measured by Mini Mental Status Questionnaire, Total Score

Mini Mental State Status questionnaire is 11 questions, total score can range from 0 to 30, with a higher score indicating better function and a negative change in baseline indicating decrease in cognitive function.

Full Information

NCT ID

NCT00509821

First Posted

July 30, 2007

Last Updated

January 9, 2019

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00509821

Brief Title

Enzastaurin Before and Concomitant With Radiation, Followed by Enzastaurin in Participants With Newly Diagnosed Glioblastoma

Official Title

Enzastaurin Before and Concomitant With Radiation Therapy, Followed by Enzastaurin Maintenance Therapy in Patients With Newly Diagnosed Glioblastoma Without Methylation of the Promoter Gene of MGMT Enzyme - a Phase II Study

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

October 2007 (undefined)

Primary Completion Date

February 2010 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the protocol was to induce a novel radiochemotherapy with enzastaurin as first-line treatment regimen in glioblastoma: Participants with active, unmethylated MGMT promoter were treated with enzastaurin before, concomitant, and after radiotherapy to determine safety and PFS at 6 months (PFS-6) in phase II.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Enzastaurin Once Daily (QD)

Arm Type

Experimental

Arm Description

Enzastaurin given orally (PO) once daily (QD). 1125 mg loading dose D(-)7 then 500 mg PO,QD with concomitant radiotherapy.

Arm Title

Enzastaurin Twice Daily (BID)

Arm Type

Experimental

Arm Description

Enzastaurin 1125 mg loading dose D(-)7 then 250 mg twice daily (BID) PO, with concomitant radiotherapy.

Intervention Type

Drug

Intervention Name(s)

Enzastaurin 500 milligram (mg) Once Daily (QD)

Other Intervention Name(s)

LY317615

Intervention Description

1125 mg loading dose D(-)7 then 500 mg QD, oral, daily until disease progression, given with and without radiotherapy treatment.

Intervention Type

Drug

Intervention Name(s)

Enzastaurin 250 mg Twice Daily (BID)

Other Intervention Name(s)

LY317615

Intervention Description

1125 mg loading dose D(-)7 then 250 mg BID, oral, daily until disease progression, given with and without radiotherapy treatment.

Primary Outcome Measure Information:

Title

Percentage of Participants With Progression Free Survival at 6 Months (PFS-6)

Description

Time Frame

Baseline to 6 months

Secondary Outcome Measure Information:

Title

Percentage of Participants With Overall Survival at 1 and 2 Years After Surgery

Description

Time Frame

Baseline to 1 and 2 year

Title

Response Rate

Description

Time Frame

Baseline to 30 months

Title

Change in Neurologic Status as Measured by Mini Mental Status Questionnaire, Total Score

Description

Time Frame

Baseline through Week 12 .

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Present with newly diagnosed histologically proven supratentorial GBM. Demonstration of an unmethylated MGMT-promotor Participants must sign an informed consent document. Participants must be at least 18 years of age. Estimated life expectancy of at least 12 weeks Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of PKC-beta targets (for example, GSK3beta). Disease evaluated by Gd-MRI (magnetic resonance imaging) within 72 hours postoperatively Interval of greater than or equal to 2 and less than or equal to 4 weeks since surgery or biopsy ECOG Performance Status of less than or equal to 2 Adequate organ function including the following: adequate bone marrow reserve: white blood cell (WBC) count greater than or equal to 3.0 X 109/L, absolute neutrophil count (ANC) greater than or equal to 1.5 X 109/L, platelet count greater than or equal to 75.0 X 109/L, and hemoglobin greater than or equal to 10.0 g/dL (greater than or equal to 6.2 mmol/L). Hepatic: bilirubin less than or equal to 1.5 times the upper limit of normal (X ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) less than or equal to 2.5 X ULN, or less than or equal to 5 X ULN with liver metastases Renal: serum creatinine less than or equal to 1.5 X ULN Blood clotting: prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits Participants must discontinue use of enzyme-inducing antiepileptic drugs (EIAEDs) greater than or equal to 14 days prior to study enrollment. The investigator may prescribe non-EIAEDs. Participants who must begin EIAED therapy while on study will be allowed to remain on study. Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG); no history of stroke Exclusion Criteria: Have a prior malignancy (other than glioblastoma, or adequately treated carcinoma in situ of the cervix, or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence Unable to undergo Gd MRI Prior chemotherapy within the last 5 years Prior chemotherapy for a brain tumor Prior radiotherapy of the head Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin History of coagulation disorder associated with bleeding, or recurrent thrombotic events Are receiving concurrent administration of anticoagulant therapy Placement of Gliadel® wafer at surgery Have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) - participants who are pregnant, anticipate becoming pregnant within 6 months after study participation, or are currently breast-feeding Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Berlin

ZIP/Postal Code

13553

Country

Germany

Facility Name

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

City

Frankfurt

ZIP/Postal Code

D-60596

Country

Germany

Facility Name

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

City

Hamburg

ZIP/Postal Code

22767

Country

Germany

Facility Name

City

Heidelberg

ZIP/Postal Code

D-69120

Country

Germany

Facility Name

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

City

Ulm

ZIP/Postal Code

89081

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

Enzastaurin Before and Concomitant With Radiation, Followed by Enzastaurin in Participants With Newly Diagnosed Glioblastoma

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