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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00509821
First received: July 30, 2007
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Glioblastoma Multiforme
Drug: enzastaurin
Radiation: radiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression free survival rate 6 months after surgery. [ Time Frame: After 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival rate at 1 and 2 years after surgery [ Time Frame: 1 and 2 year ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: baseline to progressive disease ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2007
Estimated Study Completion Date: March 2015
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Enzastaurin before and concomitant with radiotherapy followed by Enzastaurin maintenance therapy
Drug: enzastaurin

Safety Run in Regimen 1: 1125 mg loading dose D(-)7 then 500 mg QD, oral, daily until disease progression

Regimen 2: 1125 mg loading dose D(-)7 then 250 mg BID, oral, daily until disease progression

Other Name: LY317615
Radiation: radiation
Involved-field radiotherapy will be administered D1 after 7 day lead in enzastaurin treatment at a dose of 54 to 60 Gy, given in individual doses of 1.8 to 2 Gy 5 days a week for 6 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Present with newly diagnosed histologically proven supratentorial GBM.
  • Demonstration of an unmethylated MGMT-promotor
  • Patients must sign an informed consent document. Patients 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
  • Patients 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. Patients 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) - patients 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509821

Locations
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
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
  More Information

Additional Information:
No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00509821     History of Changes
Other Study ID Numbers: 11491, H6Q-MC-S039
Study First Received: July 30, 2007
Last Updated: January 31, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant 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

ClinicalTrials.gov processed this record on September 18, 2014