View Clinical Trial (Medical Research Study)
A Phase I Trial of Enzastaurin (LY317615) in Combination With Carboplatin in Adults With Recurrent Gliomas
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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Brain and Central Nervous System Tumors |
| Purpose: |
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RATIONALE: Enzastaurin may stop the growth of brain tumors by blocking blood flow to the
tumor and by blocking some of the enzymes needed for cell growth. Drugs used in
chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells,
either by killing the cells or by stopping them from dividing. Giving enzastaurin together
with carboplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of enzastaurin when
given together with carboplatin in treating patients with recurrent or refractory primary
brain tumors.
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| Study Summary: |
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OBJECTIVES:
Primary
- Determine the maximum tolerated dose of enzastaurin hydrochloride when administered
with carboplatin in patients with recurrent or refractory primary brain tumors.
- Determine the pharmacokinetics of this regimen in these patients.
Secondary
- Correlate clinical outcome with GSK3-b activation in peripheral blood mononuclear cells
of patients treated with this regimen.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of enzastaurin hydrochloride. Patients are
stratified according to concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (yes vs
no).
Patients receive oral enzastaurin hydrochloride once daily on days 1-35 and carboplatin IV
over 30 minutes on day 8 of course 1. Patients receive oral enzastaurin hydrochloride once
daily on days 1-28 and carboplatin IV over 30 minutes on day 1 in all subsequent courses.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 4-12 patients receive escalating doses of enzastaurin hydrochloride until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 3 of 4 or 5 of 12 patients experience dose-limiting toxicity.
Patients undergo blood collection on days 7 and 8 and between weeks 4-5 of course 1 for
pharmacokinetic studies. Blood is also collected at baseline and on days 7 and 28 of each
course for analysis of biological markers (PI-3 kinase, GSK3-b, and mTOR) by western blot
and other assays.
PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.
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| Criteria: |
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DISEASE CHARACTERISTICS:
- Histologically confirmed primary brain tumor, including any of the following:
- Malignant glioma, including any of the following subtypes:
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic mixed oligoastrocytoma
- Malignant glioma not otherwise specified
- Primitive neuroectodermal tumors of the CNS
- Progressive low-grade glioma
- Radiographically diagnosed brain stem glioma
- Recurrent or refractory disease
- Progressive disease after standard treatment allowed
- Must have unequivocal evidence of tumor progression by MRI or CT scan
- Steroid dosage stable for ≥ 5 days
- Must have failed prior radiotherapy
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Life expectancy > 8 weeks
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10 g/dL (transfusion allowed)
- SGOT ≤ 2 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- No significant medical illness that, in the opinion of the investigator, would
preclude study compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3-6 months after
completion of study treatment
- No known allergy to mannitol
- No other known active malignancy, except nonmelanoma skin cancer or carcinoma in situ
of the cervix
- No active infection requiring IV antibiotics
- No disease that would obscure toxicity or dangerously alter drug metabolism
- QTc < 460 msec OR measurable with Bazett's correction
- No clinically significant symptomatic arrhythmia requiring treatment, including any
of the following:
- Multifocal premature ventricular contraction
- Bigeminy
- Trigeminy
- Ventricular tachycardia, including asymptomatic sustained ventricular
tachycardia
- Bradycardia
- No history of or concurrent cardiac ischemia by EKG
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from all prior therapy, including surgery
- Prior resection of recurrent or progressive tumor allowed
- Residual disease not required
- No prior platinum-based therapy
- At least 2 weeks since prior noncytotoxic investigational agents
- At least 2 weeks since prior vincristine
- At least 3 weeks since prior procarbazine
- At least 6 weeks since prior nitrosoureas
- At least 4 weeks since prior cytotoxic therapy
- At least 4 weeks since prior and no concurrent radiotherapy
- At least 1 week since prior noncytotoxic agents, including interferon, tamoxifen,
thalidomide, or isotretinoin (radiosensitizer does not count)
- No other concurrent chemotherapy, immunotherapy, or investigational agents
- No concurrent systemic anticoagulants (e.g., heparin, warfarin, or small heparin
fragments)
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| NCT ID: |
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NCT00438997 |
| Primary Contact: |
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Principal Investigator
Howard A. Fine, MD
NCI - Neuro-Oncology Branch
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
Clinical Trials Office - Warren Grant Magnusen Clinical Center
Phone: 888-NCI-1937
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 22, 2013 |
| Modifications to this listing: |
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