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Trial record 55 of 57 for:    "Germ Cells Tumors" | "Carboplatin"

Acetylcysteine, Mannitol, Combination Chemotherapy, and Sodium Thiosulfate in Treating Children With Malignant Brain Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00238173
Recruitment Status : Terminated (OHSU IRB closed study to further enrollment 2/17/2006)
First Posted : October 13, 2005
Last Update Posted : April 21, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Neuwelt, OHSU Knight Cancer Institute

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Bone Marrow Suppression Brain and Central Nervous System Tumors Drug/Agent Toxicity by Tissue/Organ Long-term Effects Secondary to Cancer Therapy in Children Biological: filgrastim Drug: acetylcysteine Drug: carboplatin Drug: cyclophosphamide Drug: etoposide phosphate Drug: mannitol Drug: sodium thiosulfate Phase 1

Detailed Description:



  • Determine the toxicity and maximum tolerated dose of acetylcysteine when given in combination with blood-brain barrier disruption treatment with mannitol, combination chemotherapy comprising cyclophosphamide, etoposide phosphate, and carboplatin, and delayed high-dose sodium thiosulfate in pediatric patients with malignant brain tumors.


  • Determine the blood/bone marrow toxicity of this regimen in these patients.
  • Determine tumor response in patients treated with this regimen.

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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Study of N-Acetylcysteine Administered in Conjunction With Carboplatin, Cyclophosphamide, and Etoposide Phosphate BBBD, in Children With Malignant Brain Tumors
Study Start Date : December 2004
Actual Primary Completion Date : February 17, 2006
Actual Study Completion Date : February 17, 2006

Intervention Details:
  • Biological: filgrastim
  • Drug: acetylcysteine
    administered i.v. over 30 to 60 minutes
  • Drug: carboplatin
    (200 mg/m2/day; total dose 400 mg/m2) will be infused i.a. over 10 minutes, in 50-180 cc of normal saline.
  • Drug: cyclophosphamide
    (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.
  • Drug: etoposide phosphate
    (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.
  • Drug: mannitol
    (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.
  • Drug: sodium thiosulfate
    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.

Primary Outcome Measures :
  1. 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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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed brain tumors, including any of the following:

    • Brain stem glioma
    • Primitive neuroectodermal tumor
    • CNS germ cell tumor
    • Malignant glioma
  • Diagnosis based on any of the following:

    • CT-assisted or stereotactic biopsy
    • Open biopsy
    • Surgical resection
    • Cerebrospinal fluid cytology
    • Elevated tumor markers
    • Unequivocal radiographic changes (for patients with brain stem glioma or optic glioma)
  • All tumor types, except brain stem glioma, must be recurrent
  • No radiographic signs of intracranial herniation and/or spinal cord block


Performance status

  • ECOG 0-2

Life expectancy

  • At least 90 days


  • WBC ≥ 2,500/mm^3
  • Absolute granulocyte count ≥ 1,200/mm^3
  • Platelet count ≥ 100,000/mm^3


  • SGOT and SGPT < 2.5 times upper limit of normal
  • Bilirubin < 2.0 mg/dL


  • Creatinine < 1.8 mg/dL


  • No history of clinically significant reactive airway disease


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant risk for general anesthesia
  • No uncontrolled, clinically significant, confounding medical condition within the past 30 days
  • No contraindication to study drugs



  • At least 28 days since prior systemic chemotherapy


  • At least 3 months since prior total spine radiotherapy
  • At least 14 days since prior cranial radiotherapy
  • Prior systemic radiotherapy allowed


  • See Disease Characteristics

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00238173

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United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239-3098
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
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Principal Investigator: Edward A. Neuwelt, MD OHSU Knight Cancer Institute

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Responsible Party: Edward Neuwelt, Professor, OHSU Knight Cancer Institute Identifier: NCT00238173     History of Changes
Other Study ID Numbers: IRB00002050
First Posted: October 13, 2005    Key Record Dates
Last Update Posted: April 21, 2017
Last Verified: April 2017
Keywords provided by Edward Neuwelt, OHSU Knight Cancer Institute:
childhood central nervous system germ cell tumor
childhood central nervous system mixed germ cell tumor
drug/agent toxicity by tissue/organ
bone marrow suppression
long-term effects secondary to cancer therapy in children
recurrent childhood brain stem glioma
untreated childhood brain stem glioma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood brain tumor
recurrent childhood cerebellar astrocytoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
childhood oligodendroglioma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
recurrent childhood ependymoma
childhood central nervous system choriocarcinoma
childhood central nervous system embryonal tumor
childhood central nervous system germinoma
childhood central nervous system teratoma
childhood central nervous system yolk sac tumor
recurrent childhood central nervous system embryonal tumor
Additional relevant MeSH terms:
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Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sodium thiosulfate
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antiviral Agents