Portland, Oregon 97239


Purpose:

This randomized phase II trial studies how well giving combination chemotherapy with or without sodium thiosulfate works in preventing low platelet count while treating patients with malignant brain tumors. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Sodium thiosulfate may prevent low platelet counts in patients receiving chemotherapy. It is not yet known whether combination chemotherapy is more effective with or without sodium thiosulfate in preventing low platelet count during treatment for brain tumors.


Study summary:

PRIMARY OBJECTIVES: I. Determine the effect of delayed administration of sodium thiosulfate on the rates of platelet toxicity (i.e. platelet count less than 20,000), in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate. SECONDARY OBJECTIVES: I. Assess tumor response in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate, with or without delayed sodium thiosulfate. II. Assess the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts, in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate. III. Assess hearing changes, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hertz [Hz]), and at higher frequencies above standard testing (9000 to 16000 Hz). IV. Assess quality of life in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide phosphate. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cyclophosphamide intravenously (IV), etoposide phosphate IV, and carboplatin intra-arterially (IA) over 10 minutes on day 1. ARM II: Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours after carboplatin. In both arms, treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.


Criteria:

Inclusion Criteria: - Subjects with histologically confirmed high-grade glioma are eligible; diagnosis of high-grade glioma will be made on the basis of needle biopsy, open biopsy, or surgical resection - Subjects may have had prior focal or systemic radiation or chemotherapy; at least 14 days must have elapsed since radiation treatment and 28 days since prior chemotherapy - Performance status (Eastern Cooperative Oncology Group [ECOG]) must be less than or equal to 2 (Karnofsky greater than or equal to 50) - White blood cell count >= 2.5 x 10^3/mm^3 - Absolute granulocyte count >= 1.2 x 10^3/mm^3 - Platelets >= 100 x 10^3/mm^3 - Creatinine < 1.8 - Bilirubin < 2.0 - Baseline aspartate aminotransferase (AST)/alanine aminotransferase (ALT) serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) must be < 2.5 x institutional upper limits of normal - Subject (or legal guardian) must sign a written informed consent in accordance with institutional guidelines - Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform the investigator Exclusion Criteria: - Subjects with rapidly progressing central nervous system (CNS) disease with associated neurological deterioration - Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failure - Subjects who are pregnant, have a positive serum human chorionic gonadotropin (hCG) or are lactating - Subjects who have contraindications to carboplatin, cyclophosphamide, etoposide phosphate, or sodium thiosulfate


Study is Available At:


Original ID:

IRB00000922


NCT ID:

NCT00075387


Secondary ID:

NCI-2013-00781


Study Acronym:


Brief Title:

Combination Chemotherapy With or Without Sodium Thiosulfate in Preventing Low Platelet Count While Treating Patients With Malignant Brain Tumors


Official Title:

Phase II Clinical Trial of Patients With High-Grade Glioma Treated With Intra-arterial Carboplatin-Based Chemotherapy, Randomized to Treatment With or Without Delayed Intravenous Sodium Thiosulfate as a Potential Chemoprotectant Against Severe Thrombocyto


Overall Status:

Recruiting


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

75 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

OHSU Knight Cancer Institute


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

60


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Edward Neuwelt
Principal Investigator
OHSU Knight Cancer Institute

Study Dates

Start Date:March 7, 2003
Completion Date:April 30, 2021
Completion Type:Anticipated
Primary Completion Date:April 30, 2020
Primary Completion Type:Anticipated
Verification Date:May 2018
Last Changed Date:May 2, 2018
First Received Date:January 9, 2004

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Tumor response (complete response + partial response + stable disease) assessed by neurologic exams, radiographic studies, and steroid dose
Time Frame:Up to 10 years
Safety Issues:False
Description:The Pearson chi-square test will be the primary test to compare rates. Comparisons of rates will use the Pearson Chi-square test and logistic regression to adjust for potential confounders.
Outcome Type:Secondary Outcome
Measure:Time to response
Time Frame:Up to 10 years
Safety Issues:False
Description:Descriptive summaries include Kaplan-Meier plots.
Outcome Type:Secondary Outcome
Measure:Time to disease progression
Time Frame:Up to 10 years
Safety Issues:False
Description:Comparisons of time to disease progression will use the log rank test and the Cox proportional hazards model to adjust for potential confounders.
Outcome Type:Secondary Outcome
Measure:Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Quality of Life Questionnaire-Brain Module-20
Time Frame:Up to 60 days after completion of study treatment
Safety Issues:False
Description:Summarized by means over time and by plots of values over time for each patient. Quality of life data comparisons between the groups will use repeated measure analysis of covariance (baseline assessment as the covariate).
Outcome Type:Secondary Outcome
Measure:Number of dose reductions and transfusions due to platelet toxicity
Time Frame:Up to 30 days after completion of study treatment
Safety Issues:False
Description:Analyzed using generalized estimating equations and/or a generalized mixed model (for repeated measures analysis of variance) and the third using mixed model repeated measures analysis of variance model.
Outcome Type:Secondary Outcome
Measure:Granulocyte count
Time Frame:Up to 30 days after completion of study treatment
Safety Issues:False
Description:The Pearson chi-square test will be the primary test to compare rates.
Outcome Type:Secondary Outcome
Measure:Erythrocyte counts
Time Frame:Up to 30 days after completion of study treatment
Safety Issues:False
Description:The Pearson chi-square test will be the primary test to compare rates.
Outcome Type:Secondary Outcome
Measure:Change in hearing levels, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hz), and at higher frequencies above standard testing (9000 to 16000 Hz) based on American Speech-Language-Hearing Association criteria
Time Frame:Baseline up to 30 days after completion of study treatment
Safety Issues:False
Description:Descriptive summaries for hearing levels will include means by time and plots of hearing levels by patient over time. The analyses for hearing will include both a time to oto-toxicity (based on American Speech-Language-Hearing Association criteria) compar
Outcome Type:Primary Outcome
Measure:Rate of platelet toxicities (i.e. platelet count less than 20,000), graded according to the National Cancer Institute Common Toxicity Criteria version 3.0
Time Frame:Up to 4 weeks after completion of study treatment
Safety Issues:False
Description:The Pearson chi-square test will be the primary test to compare rates.

Study Interventions

Intervention Type:Drug
Name:Carboplatin
Description:Given IA
Arm Name:Arm I (combination chemotherapy)
Other Name:Blastocarb
Intervention Type:Drug
Name:Cyclophosphamide
Description:Given IV
Arm Name:Arm I (combination chemotherapy)
Other Name:(-)-Cyclophosphamide
Intervention Type:Drug
Name:Etoposide Phosphate
Description:Given IV
Arm Name:Arm I (combination chemotherapy)
Other Name:Etopophos
Intervention Type:Other
Name:Quality-of-Life Assessment
Description:Ancillary studies
Arm Name:Arm I (combination chemotherapy)
Other Name:Quality of Life Assessment
Intervention Type:Drug
Name:Sodium Thiosulfate
Description:Given IV
Arm Name:Arm II (combination chemotherapy, sodium thiosulfa
Other Name:Cyanide Antidote Package

Study Arms

Study Arm Type:Experimental
Arm Name:Arm II (combination chemotherapy, sodium thiosulfate)
Description:Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours later. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Study Arm Type:Experimental
Arm Name:Arm I (combination chemotherapy)
Description:Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:OHSU Knight Cancer Institute
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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