Phase 1/2 Study in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients - Full Text View

Sponsors and Collaborators:	Eli Lilly and Company University of California, San Francisco
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00402116

Purpose

There will be 2 phases in this study. Patients will either be enrolled to the first phase or to the second phase, depending upon when they enroll into the study.

The first phase of this study is done to evaluate the safety of enzastaurin in patients. This is done by gradually increasing the dose of the drug in small groups of patients and watching closely for side effects.

In the second phase of the study, the dose determined to be safe will be used with temozolomide during and following radiation therapy to see if the combination can help patients with brain tumors live longer.

Condition	Intervention	Phase
Glioblastoma Glioblastoma Multiforme Gliosarcoma	Drug: enzastaurin Drug: temozolomide Radiation: radiation	Phase I Phase II

Drug Information available for: Temozolomide Enzastaurin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase 1/2 Study of Enzastaurin Plus Temozolomide During and Following Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Phase 1 - To determine the maximum tolerated dose (MTD) of enzastaurin in patients with newly diagnosed GBM or GS [ Time Frame: until MTD can be deteremined ] [ Designated as safety issue: Yes ]
Phase 2 - To determine the efficacy of enzastaurin in combination with radiation therapy and temozolomide in patients with newly diagnosed GBM or GS as measured by overall survival (OS) [ Time Frame: baseline to death from any cause ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Phase 1 - To characterize the safety of enzastaurin when combined with temozolomide and radiation therapy in this setting [ Time Frame: every cycle ] [ Designated as safety issue: Yes ]
Phase 1 - To characterize the pharmacokinetics of enzastaurin when administered in combination with temozolomide and radiation therapy [ Time Frame: cycle 1, cycle 2 ] [ Designated as safety issue: No ]
Phase 1 - To assess biomarkers relevant to enzastaurin and disease state, and their correlation to clinical outcome [ Time Frame: baseline, cycle 2, end of study ] [ Designated as safety issue: No ]
Phase 1 - To assess for evidence of antitumor activity in this patient population [ Time Frame: baseline, following radiation, every other cycle ] [ Designated as safety issue: No ]
Phase 2 - To evaluate progression free survival (PFS) [ Time Frame: baseline to measured progressive disease ] [ Designated as safety issue: No ]
Phase 2 - To evaluate the safety profile of enzastaurin in combination with temozolomide and radiation therapy in this patient population [ Time Frame: every cycle ] [ Designated as safety issue: Yes ]
Phase 2 - To assess biomarkers relevant to enzastaurin and disease state and their correlation to clinical outcome [ Time Frame: baseline, cycle 2, end of study ] [ Designated as safety issue: No ]
Phase 2 - To explore the utility of magnetic resonance perfusion techniques to assess treatment with enzastaurin when possible [ Time Frame: each radiologic assessment ] [ Designated as safety issue: No ]
Phase 2 - To assess changes in health-related quality of life and symptoms in this patient population [ Time Frame: every cycle ] [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	September 2006
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Drug: enzastaurin Phase 1 - 250 mg Cohort 1 with one dose escalation allowed to 500 mg for Cohort 2, oral, daily, 6 weeks then twelve 28 day cycles Phase 2 - Phase 1 established dose, oral, daily, 6 weeks then twelve 28 day cycles Drug: temozolomide 75 mg/m2, oral, daily, 6 weeks 200 mg/m2, oral, daily, twelve 28 day cycles Radiation: radiation 1.8-2.0 Gy x 30 fractions, 5 days/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:

Patients must have a histologically confirmed diagnosis of intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS).
Biopsy or resection must have been performed no more than 5 weeks prior to treatment.
An MRI or CT scan must be obtained within 14 days prior to treatment.
Patients must not have received prior drug therapy for brain tumors.
Patients must have adequate organ function demonstrated by lab tests within 14 days prior to treatment.

Exclusion Criteria:

Patients will be excluded if unable to swallow tablets.
Patients will be excluded if unable to discontinue use of enzyme inducing antiepileptic drugs or have been off of these agents less than 2 weeks prior to treatment (i.e. phenytoin (Dilantin), carbamazepine, etc.).
Patients will be excluded if have active infection.
Patients will be excluded if have a significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
Patients will be excluded if they have concurrent therapy with an anticoagulant. If the patient requires anticoagulant therapy after starting treatment, the patient may remain on study but should be monitored carefully.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402116

Locations

United States, California
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
San Francisco, California, United States

Sponsors and Collaborators

Eli Lilly and Company

University of California, San Francisco

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

Lilly Clinical Trial Registry This link exits the ClinicalTrials.gov site

Responsible Party:	Eli Lilly ( Chief Medical Officer )
Study ID Numbers:	9815, H6Q-MC-S008
Study First Received:	November 17, 2006
Last Updated:	November 12, 2008
ClinicalTrials.gov Identifier:	NCT00402116
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Neuroectodermal Tumors
Glioblastoma
Glioblastoma multiforme
Astrocytoma
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Glioma
Gliosarcoma
Temozolomide
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009