Bone Marrow SuppressionPhase 1NCT00238173
Acetylcysteine, Mannitol, Combination Chemotherapy, and Sodium Thiosulfate in Treating Children With Malignant Brain Tumors
A Phase 1 study testing filgrastim, acetylcysteine and carboplatin in people with Bone Marrow Suppression and Brain and Central Nervous System Tumors, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Bone Marrow Suppression, Brain and Central Nervous System Tumors, Drug/Agent Toxicity by Tissue/Organ
- What is being tested?
- filgrastim, acetylcysteine and carboplatin
- Type of treatment
- Injection or infusion
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2004to 17 Feb 2006
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
OHSU Knight Cancer Institute
Portland, Oregon, 97239-3098
About this study
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
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.
Read the detailed description
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
- 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
- Being tested
- filgrastim, acetylcysteine, carboplatin, cyclophosphamide, etoposide phosphate
- 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
- Medical subject headings
- Central Nervous System Neoplasms, Drug-Related Side Effects and Adverse Reactions, Optic Nerve Glioma, Astrocytoma, Medulloblastoma, Oligodendroglioma, Familial ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
acetylcysteineDrug
administered i.v. over 30 to 60 minutes
carboplatinDrug
(200 mg/m2/day; total dose 400 mg/m2) will be infused i.a. over 10 minutes, in 50-180 cc of normal saline.
cyclophosphamideDrug
(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 phosphateDrug
(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.
mannitolDrug
(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 thiosulfateDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2005 (estimated)
- Study startDec 2004
- Primary completion17 Feb 2006
- Study completion17 Feb 2006
Why it stopped: OHSU IRB closed study to further enrollment 2/17/2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Marrow SuppressionStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Edward Neuwelt, OHSU Knight Cancer Institute
- Investigators
- Edward A. Neuwelt, MD, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00238173
- Sponsor's protocol ID
- IRB00002050
- Other IDs
- OHSU-8522, OHSU-SOL-04085-L, OHSU-IRB-2050
- Status last verified
- Apr 2017
- First submitted
- 12 Oct 2005
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00238173
- Acronym / sponsor ID
- IRB00002050
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: OHSU IRB closed study to further enrollment 2/17/2006
- Enrolment
- 2 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2004
- Primary completion
- 17 Feb 2006 (actual)
- Study completion
- 17 Feb 2006 (actual)
- First posted
- 13 Oct 2005 (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: 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.
Detailed description
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| filgrastim | Biological | – |
| acetylcysteineadministered 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 thiosulfateSTS 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. | Drug | – |
Primary outcome
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.
Results and safety
The study was stopped early (reason given: OHSU IRB closed study to further enrollment 2/17/2006). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
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Tumor Patients
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.
Edward A. Neuwelt, MD principal investigator
OHSU Knight Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing filgrastim, acetylcysteine and carboplatin in people with Bone Marrow Suppression and Brain and Central Nervous System Tumors, run by OHSU Knight Cancer Institute at 1 site 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?
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: stopped early, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was stopped early (reason given: OHSU IRB closed study to further enrollment 2/17/2006). Results are not available in the source record.
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?
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.. 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 21 Apr 2017.