Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00509821
Recruitment Status : Completed
First Posted : August 1, 2007
Results First Posted : April 5, 2019
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Drug: Enzastaurin 500 milligram (mg) Once Daily (QD) Drug: Enzastaurin 250 mg Twice Daily (BID) Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2007
Actual Primary Completion Date : February 2010
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Enzastaurin Once Daily (QD)
Enzastaurin given orally (PO) once daily (QD). 1125 mg loading dose D(-)7 then 500 mg PO,QD with concomitant radiotherapy.
Drug: Enzastaurin 500 milligram (mg) Once Daily (QD)
1125 mg loading dose D(-)7 then 500 mg QD, oral, daily until disease progression, given with and without radiotherapy treatment.
Other Name: LY317615

Experimental: Enzastaurin Twice Daily (BID)
Enzastaurin 1125 mg loading dose D(-)7 then 250 mg twice daily (BID) PO, with concomitant radiotherapy.
Drug: Enzastaurin 250 mg Twice Daily (BID)
1125 mg loading dose D(-)7 then 250 mg BID, oral, daily until disease progression, given with and without radiotherapy treatment.
Other Name: LY317615




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Percentage of Participants With Overall Survival at 1 and 2 Years After Surgery [ Time Frame: Baseline to 1 and 2 year ]
    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.

  2. Response Rate [ Time Frame: Baseline to 30 months ]
    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.

  3. Change in Neurologic Status as Measured by Mini Mental Status Questionnaire, Total Score [ Time Frame: Baseline through Week 12 . ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00509821


Locations
Layout table for location information
Germany
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, Germany, 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, Germany, 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, Germany, 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, Germany, 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, Germany, 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, Germany, 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, Germany, 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, Germany, 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, Germany, 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, Germany, 89081
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Layout table for investigator information
Study Director: 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) Eli Lilly and Company

Additional Information:
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00509821    
Other Study ID Numbers: 11491
H6Q-MC-S039 ( Other Identifier: Eli Lilly and Company )
First Posted: August 1, 2007    Key Record Dates
Results First Posted: April 5, 2019
Last Update Posted: April 5, 2019
Last Verified: January 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue