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

NCT00402116 | Completed Phase 1 Results

• 2 other identifiers: 9815H6Q-MC-S008
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Phase 1- Determination of the Maximum Tolerated Dose (MTD) of Enzastaurin

  Phase 1- dose escalation of enzastaurin in 2 cohorts up to 6 participants each in order to assess MTD. After radiation/enzastaurin 250 mg per day/temozolomide 75 mg/m\^2 therapy, if no more than 1 of 6 patients experienced a dose-limiting toxicity (DLT) or tumor progression, participants completed one 28-day cycle. If no significant toxicity after the first cycle, participants received subsequent cycles. If no more than 1 of the 6 patients treated at 250 mg of enzastaurin experienced a DLT, up to 6 more patients could be entered at escalated dose cohort of enzastaurin (500 mg).

  Until MTD can be determined (up to 12 cycles, 28 days per cycle)

• Phase 1 and Phase 2 - Overall Survival (OS)

  OS is the time from surgical diagnosis to the date of death from any cause. For participants who were alive, OS was censored at the last contact.

  Baseline to death from any cause (Up to 48 weeks)

Secondary Outcomes (10)

• Phase 1 - Number of Participants With Adverse Events (AEs)

  Every cycle (up to 12 cycles, 28 days per cycle)

• Phase 1 and 2: Association Between Biomarkers and Clinical Outcome

  Baseline, Cycle 2, end of study (up to 12 cycles, 28 days per cycle)

• Phase 1 - Response Rate With Macdonald Criteria

  Baseline, following radiation, every other cycle (up to 12 cycles, 28 days per cycle)

• Phase 2 - Number of Participants With Adverse Events (AEs)

  Every cycle (28 days per cycle)

• Number of Participants Undergoing Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS) for Clinical Evaluation at Baseline

  Each radiologic assessment (up to 12 cycles, 28 days per cycle)

Study Arms (1)

A

EXPERIMENTAL

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.

Drug: enzastaurin; Drug: temozolomide; Radiation: radiation therapy

Interventions

enzastaurin 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

Also known as: LY317615

A

temozolomide DRUG

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

A

radiation therapy RADIATION

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

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• University of California, San Francisco: collaborator

Study Sites (1)

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

Location

Related Links

• Lilly Clinical Trial Registry

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

enzastaurin; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2006
• First Posted: November 22, 2006
• Study Start: September 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 6, 2020
• Results First Posted: August 6, 2020

Record last verified: 2020-07

Locations

US (1)