Glioblastoma MultiformePhase 2NCT00509821

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

A Phase 2 study testing Enzastaurin 500 milligram (mg) Once Daily (QD) and Enzastaurin 250 mg Twice Daily (BID) in people with Glioblastoma Multiforme, run by Eli Lilly and Company at 10 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma Multiforme
What is being tested?: Enzastaurin 500 milligram (mg) Once Daily (QD) and Enzastaurin 250 mg Twice Daily (BID)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 10 sitesGermany
Study dates: Oct 2007to Mar 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

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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

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

Germany10 sites

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.
Berlin, 13553
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.
Erlangen, 91054
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.
Frankfurt, D-60596
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.
Freiburg im Breisgau, 79106
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.
Hamburg, 22767
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.
Heidelberg, D-69120
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.
Leipzig, 04103
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.
Mannheim, 68167
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.
Regensburg, 93053
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.
Ulm, 89081

Other trials in Germany

About this study

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

Conditions: Glioblastoma Multiforme
Being tested: Enzastaurin 500 milligram (mg) Once Daily (QD), Enzastaurin 250 mg Twice Daily (BID)
Medical subject headings: Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Enzastaurin 500 milligram (mg) Once Daily (QD)Drug
Also called LY317615
1125 mg loading dose D(-)7 then 500 mg QD, oral, daily until disease progression, given with and without radiotherapy treatment.
Enzastaurin 250 mg Twice Daily (BID)Drug
Also called LY317615
1125 mg loading dose D(-)7 then 250 mg BID, oral, daily until disease progression, given with and without radiotherapy treatment.

Study groups in NCT00509821
Study group	Role	What they receive
Enzastaurin Once Daily (QD)	Experimental	Enzastaurin given orally (PO) once daily (QD). 1125 mg loading dose D(-)7 then 500 mg PO,QD with concomitant radiotherapy. Receives: Drug: Enzastaurin 500 milligram (mg) Once Daily (QD)
Enzastaurin Twice Daily (BID)	Experimental	Enzastaurin 1125 mg loading dose D(-)7 then 250 mg twice daily (BID) PO, with concomitant radiotherapy. Receives: Drug: Enzastaurin 250 mg Twice Daily (BID)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to 6 months

Secondary outcomes (3)

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.
Measured: Baseline to 1 and 2 year
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.
Measured: Baseline to 30 months
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.
Measured: Baseline through Week 12 .

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2007Mar 2016

First posted1 Aug 2007 (estimated)
Study startOct 2007
Primary completionFeb 2010
Study completionMar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00509821
Sponsor's protocol ID: 11491
Other IDs: H6Q-MC-S039
Status last verified: Jan 2019
First submitted: 30 Jul 2007
Last updated: 5 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
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Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
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RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

All Glioblastoma Multiforme trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00509821
Acronym / sponsor ID: 11491
Conditions: Glioblastoma Multiforme
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Oct 2007
Primary completion: Feb 2010 (actual)
Study completion: Mar 2016 (actual)
First posted: 1 Aug 2007 (estimated)
Results: Posted 5 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Enzastaurin Once Daily (QD)	Experimental	Drug: Enzastaurin 500 milligram (mg) Once Daily (QD)Enzastaurin given orally (PO) once daily (QD). 1125 mg loading dose D(-)7 then 500 mg PO,QD with concomitant radiotherapy.
Enzastaurin Twice Daily (BID)	Experimental	Drug: Enzastaurin 250 mg Twice Daily (BID)Enzastaurin 1125 mg loading dose D(-)7 then 250 mg twice daily (BID) PO, with concomitant radiotherapy.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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).

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Enzastaurin 500 milligram (mg) Once Daily (QD)Also: LY3176151125 mg loading dose D(-)7 then 500 mg QD, oral, daily until disease progression, given with and without radiotherapy treatment.	Drug	Enzastaurin Once Daily (QD)
Enzastaurin 250 mg Twice Daily (BID)Also: LY3176151125 mg loading dose D(-)7 then 250 mg BID, oral, daily until disease progression, given with and without radiotherapy treatment.	Drug	Enzastaurin Twice Daily (BID)

Primary outcome

Percentage of Participants With Progression Free Survival at 6 Months (PFS-6)
Time frame: Baseline to 6 months
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.

3 secondary outcomes

Percentage of Participants With Overall Survival at 1 and 2 Years After Surgery
Time frame: Baseline to 1 and 2 year
Response Rate
Time frame: Baseline to 30 months
Change in Neurologic Status as Measured by Mini Mental Status Questionnaire, Total Score
Time frame: Baseline through Week 12 .

Results and safety

Results posted to the registry on 5 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Enzastaurin Once Daily (QD)	3	3
Enzastaurin Twice Daily (BID)	57	53

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

Time frame: Baseline to 6 months. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Enzastaurin Twice Daily (BID) n = 57
Value	53.6 (39.8 to 65.6)

Population analysed: All participants in BID arm who received at least one dose of study drug, BID, 4 participants were censored. Enzastaurin QD participants data not collected, as per protocol.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose of study drug through 4 years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Induction Enzastaurin Once Daily (QD)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Induction Enzastaurin Twice Daily (BID)	5 of 57 (8.8%)	22 of 57 (38.6%)	Not reported
Radiation Enzastaurin Once Daily (QD)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Radiation Enzastaurin Twice Daily (BID)	16 of 53 (30.2%)	43 of 53 (81.1%)	Not reported
Maintenance Enzastaurin Once Daily (QD)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Maintenance Enzastaurin Twice Daily (BID)	8 of 49 (16.3%)	28 of 49 (57.1%)	Not reported
Enzastaurin Once Daily (QD) Entire Study	0 of 3 (0%)	3 of 3 (100%)	Not reported
Enzastaurin Twice Daily (BID) Entire Study	27 of 57 (47.4%)	50 of 57 (87.7%)	Not reported

Limitations and caveats (from the sponsor): 3 participants receiving 500 mg enzastaurin qd were not included in analysis for outcome measures per protocol.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Lilly Clinical Trial RegistryLink provided by the sponsor.

Related trials for Glioblastoma Multiforme

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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) study director

Eli Lilly and Company

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Progression Free Survival at 6 Months (PFS-6) (time frame: Baseline to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00509821.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2019.