Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients

NCT ID: NCT00402116

Last Updated: 2020-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-12-31

Brief Summary

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.

Conditions

Glioblastoma; Glioblastoma Multiforme; Gliosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

The Phase 1 consisted of the dose escalation of enzastaurin in 2 cohorts of up to 6 patients to assess maximum tolerated dose (MTD). Cohort 1 = radiotherapy/enzastaurin 250 mg per day/temozolomide 75 mg/m\^2 therapy. The 6 initial cohort patients were clinically evaluated for dose-limiting toxicities (DLT). If no more than 1 of 6 patients experienced a DLT or tumor progression, patients continued 1 complete adjuvant enzastaurin/temozolomide 28-day cycle. If there was no significant toxicity after the first adjuvant cycle, participants received subsequent adjuvant enzastaurin/temozolomide cycles. If no more than 1 of the 6 initial cohort participants treated at 250 mg of enzastaurin experienced a DLT during radiotherapy and the first adjuvant cycle, up to 6 more participants could be entered at 500 mg of enzastaurin. The Phase 2, using the MTD determined in the Phase 1 (250 mg), evaluated the combination's safety and measured OS.

Group Type: EXPERIMENTAL

enzastaurin

Intervention Type: DRUG

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

temozolomide

Intervention Type: DRUG

75 milligrams per meter squared (mg/m\^2), oral, daily, 6 weeks then 200 mg/m\^2, oral, daily, twelve 28 day cycles

radiation therapy

Intervention Type: RADIATION

1.8-2.0 Gy x 30 fractions, 5 days/week, for 6 weeks

Interventions

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

Intervention Type: DRUG

temozolomide

75 milligrams per meter squared (mg/m\^2), oral, daily, 6 weeks then 200 mg/m\^2, oral, daily, twelve 28 day cycles

Intervention Type: DRUG

radiation therapy

1.8-2.0 Gy x 30 fractions, 5 days/week, for 6 weeks

Intervention Type: RADIATION

Other Intervention Names

LY317615

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

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

San Francisco, California, United States

Countries

United States

Other Identifiers

H6Q-MC-S008

Identifier Type: OTHER

Identifier Source: secondary_id

9815

Identifier Type: -

Identifier Source: org_study_id