Phase I and Pharmacokinetic Study of Enzastaurin (LY317615) in Children and Adolescents With Refractory Primary CNS Tumors
- 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.
- Histologically confirmed primary CNS malignancy including low-grade glioma
- All tumors, except intrinsic brain stem and diffuse optic pathway tumors, must
have histological verification at either the time of diagnosis or recurrence
- Patients with intrinsic brain stem or diffuse optic pathway tumors must
have clinical and/or radiographic evidence of progression
- Recurrent or progressive disease or disease refractory to standard therapy and for
which there is no known curative therapy
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
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.
First 28 days of therapy
Susan M. Blaney, MD
Texas Children's Cancer Center
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|
|UCSF Medical Center at Parnassus||San Francisco, California 94143-0296|