Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors
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|ClinicalTrials.gov Identifier: NCT00503724|
Recruitment Status : Completed
First Posted : July 19, 2007
Last Update Posted : March 6, 2012
RATIONALE: Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of enzastaurin in treating young patients with refractory primary brain tumors.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors Neuroblastoma||Drug: enzastaurin hydrochloride||Phase 1|
- To estimate the maximum tolerated dose (MTD) and/or recommend a phase II dose of enzastaurin hydrochloride in children with recurrent or refractory CNS tumors who are not receiving enzyme-inducing anticonvulsants.
- To further characterize the pharmacokinetics and toxicity of the recommended phase II dose of enzastaurin hydrochloride given twice daily in these patients.
- To characterize the pharmacokinetics of enzastaurin hydrochloride at the recommended phase II dose given once a day or twice a day in children.
- To document and describe toxicities associated with enzastaurin hydrochloride.
- To document antitumor activity in children with recurrent or refractory CNS tumors.
- To explore changes in MR perfusion scans obtained within 15 ± 2 days after initiation of enzastaurin hydrochloride therapy as compared to baseline and to correlate these changes with clinical outcome.
- To evaluate a panel of biological surrogate markers in this patient population at baseline and following enzastaurin hydrochloride administration.
OUTLINE: This is a multicenter study.
Patients receive oral enzastaurin hydrochloride once daily until the maximum tolerated dose (MTD) is determined. Patients then receive enzastaurin hydrochloride at the MTD twice daily on days 1-28. Treatment repeats every 28 days for 13 courses in the absence of disease progression or unacceptable toxicity. Patients may receive 13 additional courses (for a total of 26 courses) of oral enzastaurin hydrochloride if the patient is benefitting from the treatment and the investigator and subject agree to continue treatment.
Patients undergo blood sample collection periodically for pharmacokinetic studies.
After completion of study treatment, patients are followed periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I and Pharmacokinetic Study of Enzastaurin (LY317615) in Children and Adolescents With Refractory Primary CNS Tumors|
|Study Start Date :||June 2007|
|Actual Primary Completion Date :||May 2010|
|Actual Study Completion Date :||May 2010|
- Drug: enzastaurin hydrochloride
Participants receive 200, 260, 340, or 440 mg/m2/day of enzastaurin orally once daily for 28 days (one course) during the dose escalation phase of the study. To study the toxicity profile of the MTD or phase II recommended dose established during the dose escalation phase, participants receive twice daily doses of enzastaurin orally at the phase II recommended dose for 28 days (one course). In the absence of unacceptable toxicity or disease progression, treatment may continue for 13 courses (approximately one year).Other Name: LY317615 monohydrochloride
- Maximum tolerated dose [ Time Frame: First 28 days of therapy ]The maximum tolerated dose or recommended phase II dose will be based on the dose-limiting toxicities observed during the first 28 days of therapy in those participants receiving enzastaurin on a once per day dosing schedule.
- Number of participants treated with the maximum tolerated dose or phase II recommended dose on a twice daily dosage schedule with dose-limiting toxicities [ Time Frame: First 28 days of therapy ]
- Pharmacokinetics [ Time Frame: Three days prior to course 1 and day 28 of course 1 ]Blood samples for pharmacokinetic studies will be drawn 3 days prior to course 1 and on day 28 of course 1.
- Toxicity [ Time Frame: From day 1 of therapy until 30 days after the last dose of the drug ]
- Tumor response [ Time Frame: Pre-treatment, day 15 of course 1, and at the end of courses 3, 5, 8, 11, and 13. ]Brain images to assess tumor response (complete response, partial response, or stable disease) are taken pre-treatment, at day 15 of course 1, and at the end of courses 3, 5, 8, 11, and 13.
- Change in MR perfusion parameters obtained within 15 ± 2 days after initiation of enzastaurin hydrochloride therapy as compared to baseline [ Time Frame: Baseline and day 15 of course 1 ]
- Change from baseline in the inhibition of Akt cell signaling at day 14 and day 28 [ Time Frame: Pre-treatment and at days 14 and 28 of course 1 ]
- Akt pathway activity in pre-study tumor samples [ Time Frame: Pre-treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00503724
|United States, California|
|UCSF Medical Center at Parnassus|
|San Francisco, California, United States, 94143-0372|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Illinois|
|Children's Memorial Hospital - Chicago|
|Chicago, Illinois, United States, 60614|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital|
|Houston, Texas, United States, 77030-2399|
|Study Chair:||Susan M. Blaney, MD||Texas Children's Cancer Center|