Brain and Central Nervous System TumorsPhase 1NCT00503724
Enzastaurin in Treating Young Patients With Refractory Primary CNS Tumors
A Phase 1 study testing enzastaurin hydrochloride in people with Brain and Central Nervous System Tumors and Neuroblastoma, run by Pediatric Brain Tumor Consortium at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Neuroblastoma
- What is being tested?
- enzastaurin hydrochloride
- Type of treatment
- Pill or oral medicine
- How many people
- 32 participants
- Where
- 8 sitesUnited States
- Study dates
- Jun 2007to May 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
- 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
Who cannot join
- 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:
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- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60614
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, 77030-2399
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
UCSF Medical Center at Parnassus
San Francisco, California, 94143-0372
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
About this study
Official title: Phase I and Pharmacokinetic Study of Enzastaurin (LY317615) in Children and Adolescents With Refractory Primary CNS Tumors
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.
Read the detailed description
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
- Being tested
- enzastaurin hydrochloride
- 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
- Medical subject headings
- Central Nervous System Neoplasms, Neuroblastoma, Astrocytoma, Choroid Plexus Neoplasms, Familial ependymoma, Medulloblastoma, Oligodendroglioma, Optic Nerve Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enzastaurin hydrochlorideDrug
Also called LY317615 monohydrochloride
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).
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: First 28 days of therapy
Secondary outcomes (6)
Pharmacokinetics
Blood samples for pharmacokinetic studies will be drawn 3 days prior to course 1 and on day 28 of course 1.
Measured: Three days prior to course 1 and day 28 of course 1
Toxicity
Measured: From day 1 of therapy until 30 days after the last dose of the drug
Tumor response
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.
Measured: 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
Measured: Baseline and day 15 of course 1
Change from baseline in the inhibition of Akt cell signaling at day 14 and day 28
Measured: Pre-treatment and at days 14 and 28 of course 1
Akt pathway activity in pre-study tumor samples
Measured: Pre-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2007 (estimated)
- Study startJun 2007
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Susan M. Blaney, MD, Study chair, Texas Children's Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00503724
- Sponsor's protocol ID
- CDR0000557572
- Other IDs
- U01CA081457, PBTC-023
- Status last verified
- Mar 2012
- First submitted
- 17 Jul 2007
- Last updated
- 6 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I and Pharmacokinetic Study of Enzastaurin (LY317615) in Children and Adolescents With Refractory Primary CNS Tumors
- ClinicalTrials.gov ID
- NCT00503724
- Acronym / sponsor ID
- CDR0000557572
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2007
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 19 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- 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.
Secondary
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (29 listed)
- 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:
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enzastaurin hydrochlorideAlso: LY317615 monohydrochlorideParticipants 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). | Drug | – |
Primary outcome
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
6 secondary outcomes
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.
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan M. Blaney, MD study chair
Texas Children's Cancer Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing enzastaurin hydrochloride in people with Brain and Central Nervous System Tumors and Neuroblastoma, run by Pediatric Brain Tumor Consortium at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: First 28 days of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2012.