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| ID | Type | Description | Link |
|---|---|---|---|
| OHSU-8522 | |||
| OHSU-SOL-04085-L | |||
| OHSU-IRB-2050 |
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OHSU IRB closed study to further enrollment 2/17/2006
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, etoposide phosphate, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Mannitol may help chemotherapy work better by making it easier for these drugs to get to the tumor. Chemoprotective drugs, such as acetylcysteine and sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Giving acetylcysteine together with mannitol, combination chemotherapy, and sodium thiosulfate may be an effective treatment for malignant brain tumors.
PURPOSE: This phase I trial is studying the side effects and best dose of acetylcysteine when given together with mannitol, combination chemotherapy, and sodium thiosulfate in treating children with malignant brain tumors.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a dose-escalation study of acetylcysteine.
Patients receive acetylcysteine IV over 30-60 minutes followed, at least 15 minutes later, by x-ray-guided femoral artery catheterization under general anesthesia on days 1 and 2. After placement of the catheter, patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes, mannitol intra-arterially (IA) over 30 seconds, and carboplatin IA over 10 minutes also on days 1 and 2. Patients then receive high-dose sodium thiosulfate IV over 15 minutes 4 hours after completion of carboplatin. Some patients may receive a second dose of sodium thiosulfate 8 hours after completion of carboplatin. Beginning 48 hours after the last dose of chemotherapy on day 2, patients receive filgrastim (G-CSF) subcutaneously once daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of acetylcysteine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 3 patients are treated at the MTD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| filgrastim | Biological | |||
| acetylcysteine | Drug | administered i.v. over 30 to 60 minutes | ||
| carboplatin | Drug | (200 mg/m2/day; total dose 400 mg/m2) will be infused i.a. over 10 minutes, in 50-180 cc of normal saline. | ||
| cyclophosphamide | Drug | (330 mg/m2/day; total dose 660 mg/m2) will be infused i.v. in 25-50 cc of normal saline, over approximately 10 minutes. | ||
| etoposide phosphate | Drug | (200 mg/m2/day; total dose 400 mg/m2) will be infused i.v. in 25-100 cc of normal saline, over approximately 10 minutes, immediately following the cyclophosphamide. | ||
| mannitol |
| Measure | Description | Time Frame |
|---|---|---|
| To assess toxicity and the maximally tolerated dose of N-acetylcysteine administered in conjunction with carboplatin, cyclophosphamide and etoposide phosphate BBBD, and delayed high dose sodium thiosulfate, in children with malignant brain tumors. |
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DISEASE CHARACTERISTICS:
Histologically confirmed brain tumors, including any of the following:
Diagnosis based on any of the following:
All tumor types, except brain stem glioma, must be recurrent
No radiographic signs of intracranial herniation and/or spinal cord block
PATIENT CHARACTERISTICS:
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Pulmonary
Other
PRIOR CONCURRENT THERAPY:
Chemotherapy
Radiotherapy
Surgery
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| Name | Affiliation | Role |
|---|---|---|
| Edward A. Neuwelt, MD | OHSU Knight Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| OHSU Knight Cancer Institute | Portland | Oregon | 97239-3098 | United States |
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(25%) delivered i.a. at a pre-determined flow rate over 30 seconds. The flow rate will be determined by iodinated contrast injection and fluoroscopy as the lowest infusion rate in which there is retrograde flow from the arterial catheter. The rate and volume of mannitol infused will be approximately 4-12 cc/sec x 30 seconds. |
| sodium thiosulfate | Drug | STS is available as a 25% (250 mg/ml) solution. The dose of STS administered 4 hours after carboplatin is 16 gm/m2. The dose of STS administered 8 hours after carboplatin is 16 gm/m2. Actual dose to be administered will be determined and mixed with an equivalent amount of sterile water (1 ml:1 ml) for infusion. |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D020339 | Optic Nerve Glioma |
| D001254 | Astrocytoma |
| D008527 | Medulloblastoma |
| D009837 | Oligodendroglioma |
| C531673 | Familial ependymoma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D064419 | Chemically-Induced Disorders |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D019574 | Optic Nerve Neoplasms |
| D003390 | Cranial Nerve Neoplasms |
| D010524 | Peripheral Nervous System Neoplasms |
| D003389 | Cranial Nerve Diseases |
| D009901 | Optic Nerve Diseases |
| D005128 | Eye Diseases |
| D018242 | Neuroectodermal Tumors, Primitive |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D000111 | Acetylcysteine |
| D016190 | Carboplatin |
| D003520 | Cyclophosphamide |
| C061400 | etoposide phosphate |
| D008353 | Mannitol |
| C017717 | sodium thiosulfate |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D056831 | Coordination Complexes |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
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