Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors

NCT00503724 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000557572U01CA081457PBTC-023
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors; Neuroblastoma

Keywords

recurrent childhood brain stem glioma; childhood central nervous system germ cell tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; childhood choroid plexus tumor; childhood craniopharyngioma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; childhood oligodendroglioma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood visual pathway and hypothalamic glioma; recurrent childhood visual pathway glioma; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood subependymal giant cell astrocytoma; recurrent childhood pineoblastoma; recurrent childhood brain tumor; disseminated neuroblastoma; recurrent neuroblastoma

Outcome Measures

Primary Outcomes (2)

• 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

• Number of participants treated with the maximum tolerated dose or phase II recommended dose on a twice daily dosage schedule with dose-limiting toxicities

  First 28 days of therapy

Secondary Outcomes (6)

• Pharmacokinetics

  Three days prior to course 1 and day 28 of course 1

• Toxicity

  From day 1 of therapy until 30 days after the last dose of the drug

• Tumor response

  Pre-treatment, 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

  Baseline and day 15 of course 1

• Change from baseline in the inhibition of Akt cell signaling at day 14 and day 28

  Pre-treatment and at days 14 and 28 of course 1

Interventions

enzastaurin hydrochloride DRUG

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).

Also known as: LY317615 monohydrochloride

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Karnofsky performance scale (for \> 16 years of age) or Lansky performance score (for ≤ 16 years of age) ≥ 60% assessed within two weeks prior to registration
• Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
• Platelet count ≥ 100,000/μL (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age as follows:
• mg/dL (≤ 5 years of age)
• mg/dL (6 to 10 years of age)
• mg/dL (11 to 15 years of age)
• mg/dL (≥ 16 years of age)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
• ALT ≤ 5 x ULN for age
• Serum albumin ≥ 2.5 g/dL
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
• Negative pregnancy test
• Patients must have a normal QTc for age and no evidence of a clinically significant arrhythmia on ECG

You may not qualify if:

• Pregnant or lactating
• Body surface area \< 0.5 m\^2
• Clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
• Known hypersensitivity to enzastaurin hydrochloride or its components
• Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
• PRIOR CONCURRENT THERAPY:
• Must have recovered from the acute toxic effects (grade ≤ 2) of all prior therapy before entering this study
• Must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (6 weeks for prior nitrosourea)
• At least 7 days since the completion of therapy with a hematopoietic growth agent (i.e., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or erythropoietin)
• At least 14 days since long-acting formulations
• Therapeutic use of myeloid growth factors in patients with serious neutropenic conditions, such as sepsis, may be considered at the investigator's discretion
• At least 7 days since the completion of therapy with a biologic agent
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 6 months must have elapsed after prior total body irradiation (TBI) or craniospinal radiotherapy
• At least 6 weeks must have elapsed after other substantial bone marrow irradiation

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

UCSF Medical Center at Parnassus

San Francisco, California, 94143-0372, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Neuroblastoma; Astrocytoma; Choroid Plexus Neoplasms; Familial ependymoma; Medulloblastoma; Oligodendroglioma; Optic Nerve Glioma

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Glioma; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases

Study Officials

• Susan M. Blaney, MD

  Texas Children's Cancer Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 17, 2007
• First Posted: July 19, 2007
• Study Start: June 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: March 6, 2012

Record last verified: 2012-03

Locations

US (8)