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

NCT00238173 | Terminated Phase 1 DMC

• 4 other identifiers: IRB00002050OHSU-8522OHSU-SOL-04085-LOHSU-IRB-2050
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Bone Marrow Suppression; Brain and Central Nervous System Tumors; Drug/Agent Toxicity by Tissue/Organ; Long-term Effects Secondary to Cancer Therapy in Children

Keywords

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; childhood central nervous system germ cell tumor; 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 mixed germ cell tumor; childhood central nervous system teratoma; childhood central nervous system yolk sac tumor; recurrent childhood central nervous system embryonal tumor

Outcome Measures

Primary Outcomes (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.

Interventions

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 DRUG

(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.

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: Performance status * ECOG 0-2 Life expectancy * At least 90 days Hematopoietic * WBC ≥ 2,500/mm\^3 * Absolute granulocyte count ≥ 1,200/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * SGOT and SGPT \< 2.5 times upper limit of normal * Bilirubin \< 2.0 mg/dL Renal * Creatinine \< 1.8 mg/dL Pulmonary * No history of clinically significant reactive airway disease Other * 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 PRIOR CONCURRENT THERAPY: Chemotherapy * At least 28 days since prior systemic chemotherapy Radiotherapy * At least 3 months since prior total spine radiotherapy * At least 14 days since prior cranial radiotherapy * Prior systemic radiotherapy allowed Surgery * See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Drug-Related Side Effects and Adverse Reactions; Optic Nerve Glioma; Astrocytoma; Medulloblastoma; Oligodendroglioma; Familial ependymoma

Interventions

Filgrastim; Acetylcysteine; Carboplatin; Cyclophosphamide; etoposide phosphate; Mannitol; sodium thiosulfate

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Chemically-Induced Disorders; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Coordination Complexes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Sugar Alcohols; Alcohols

Study Officials

• Edward A. Neuwelt, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 12, 2005
• First Posted: October 13, 2005
• Study Start: December 1, 2004
• Primary Completion: February 17, 2006
• Study Completion: February 17, 2006
• Last Updated: April 21, 2017

Record last verified: 2017-04

Locations

US (1)