Clinical trial NCT00402116: Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients
Official title: Phase 1/2 Study of Enzastaurin Plus Temozolomide During and Following Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Glioblastoma Multiforme
Gliosarcoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: University of California, San Francisco
First posted: 2006-11-22
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Phase 1- Determination of the Maximum Tolerated Dose (MTD) of Enzastaurin
timeFrame: Until MTD can be determined (up to 12 cycles, 28 days per cycle)
measure: Phase 1 and Phase 2 - Overall Survival (OS)
timeFrame: Baseline to death from any cause (Up to 48 weeks)
Secondary outcomes:
measure: Phase 1 - Number of Participants With Adverse Events (AEs)
timeFrame: Every cycle (up to 12 cycles, 28 days per cycle)
measure: Phase 1 and 2: Association Between Biomarkers and Clinical Outcome
timeFrame: Baseline, Cycle 2, end of study (up to 12 cycles, 28 days per cycle)
measure: Phase 1 - Response Rate With Macdonald Criteria
timeFrame: Baseline, following radiation, every other cycle (up to 12 cycles, 28 days per cycle)
measure: Phase 2 - Number of Participants With Adverse Events (AEs)
timeFrame: Every cycle (28 days per cycle)
measure: Number of Participants Undergoing Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS) for Clinical Evaluation at Baseline
timeFrame: Each radiologic assessment (up to 12 cycles, 28 days per cycle)
measure: Phase 1 and 2 - Progression-Free Survival (PFS)
timeFrame: Baseline to measured progressive disease (up to 12 cycles, 28 days per cycle)
measure: Functional Assessment of Cancer Therapy - Brain (FACT-Br)
timeFrame: Every cycle (up to 12 cycles, 28 days per cycle)
measure: M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
timeFrame: Every cycle (up to 12 cycles, 28 days per cycle)
measure: Phase 1- Pharmacokinetics (PK): Maximum Observed Drug Concentration During 1 Dosing Interval at Steady State (Cmax,ss) for Enzastaurin, LY326020, and Total Analyte (Enzastaurin + LY326020) When Enzastaurin Administered With or Without Temozolomide
timeFrame: Cycle 1 Day 22, Cycle 2 Day 5, 28 days per Cycle
measure: Phase 1 and 2- Pharmacokinetics: Area Under the Concentration-Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) for Enzastaurin, LY326020 and Total Analyte (Enzastaurin + LY326020) When Enzastaurin Administered With or Without Temozolomide
timeFrame: Phase 1, Cycle 1 Day 22, Cycle 2 Day 5 of a 28 day Cycle; Phase 2, Cycle 1 Day 22 of a 28 day Cycle
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: 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
state: California
Study officials:
affiliation: Eli Lilly and Company
name: 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
References: