Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00503724
• Date of registration: 17/07/2007
• Primary sponsor: Pediatric Brain Tumor Consortium
• Public title: Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors
• Scientific title: Phase I and Pharmacokinetic Study of Enzastaurin (LY317615) in Children and Adolescents With Refractory Primary CNS Tumors
• Date of first enrolment: June 2007
• Target sample size: 32
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00503724
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Susan M. Blaney, MD
• Affiliation: Texas Children's Cancer Center

Key inclusion & exclusion criteria

DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

Inclusion Criteria:

- 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:

- 0.8 mg/dL (= 5 years of age)

- 1.0 mg/dL (6 to 10 years of age)

- 1.2 mg/dL (11 to 15 years of age)

- 1.5 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

- No evidence of active graft-versus-host disease

Exclusion Criteria:

- 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:

Inclusion Criteria:

- 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

- At least 6 months since prior allogeneic bone marrow transplantation

- At least 3 months since prior autologous bone marrow or stem cell transplantation

- Patients who are receiving dexamethasone must be on a stable or decreasing dose for
at least 1 week prior to registration

- Corticosteroids should be used at the lowest dose to control symptoms of edema
and mass effect

Exclusion Criteria:

- Routine concurrent use of growth factors (i.e., G-CSF, GM-CSF, or erythropoietin)

- Any other concurrent anticancer or investigational drug therapy

- Concurrent enzyme-inducing anticonvulsants (EIACDs)

- Concurrent gents that prolong the QTc

- Concurrent drugs that are substrates or inhibitors of CYP3A4 or CYP2C9

- Other concurrent drugs that are sensitive substrates of CYP2C8, CYP2C9, or CYP2C19
and/or have a narrow therapeutic window



Age minimum: N/A
Age maximum: 21 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Brain and Central Nervous System Tumors

Neuroblastoma

Intervention(s)

Drug: enzastaurin hydrochloride

Primary Outcome(s)

Maximum tolerated dose [Time Frame: 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 [Time Frame: First 28 days of therapy]

Secondary Outcome(s)

Akt pathway activity in pre-study tumor samples [Time Frame: Pre-treatment]

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]

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]

Pharmacokinetics [Time Frame: Three days prior to course 1 and 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.]

Secondary ID(s)

CDR0000557572

PBTC-023

U01CA081457

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)