Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Text Size

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00075387
First received: January 9, 2004
Last updated: May 25, 2016
Last verified: May 2016
History of Changes
  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.

Condition Intervention Phase
Glioma
 Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Etoposide Phosphate
Other: Quality-of-Life Assessment
Drug: Sodium Thiosulfate
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Supportive Care
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 Thrombocytopenia

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Rate of platelet toxicities (ie. platelet count less than 20,000), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    The Pearson chi-square test will be the primary test to compare rates.


Secondary Outcome Measures:
  • 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 (ASHA) criteria [ Time Frame: Baseline up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
    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 ASHA criteria) comparison using the log rank test and a repeated measure analysis of covariance of the actual hearing levels (with baseline hearing levels as the covariate). Separate analyses will be performed for each hearing frequency with no adjustment for multiple comparisons (as these analyses are descriptive in nature).

  • Erythrocyte counts [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
    The Pearson chi-square test will be the primary test to compare rates.

  • Granulocyte count [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
    The Pearson chi-square test will be the primary test to compare rates.

  • Number of dose reductions and transfusions due to platelet toxicity [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
    Analyzed using generalized estimating equations (GEE) and/or a generalized mixed model (for repeated measures analysis of variance [ANOVA]) and the third using mixed model repeated measures ANOVA model.

  • Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and QLQ-Brain Module (BN)-20 [ Time Frame: Up to 60 days after completion of study treatment ] [ Designated as safety issue: No ]
    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).

  • Time to disease progression [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Comparisons of time to disease progression will use the log rank test and the Cox proportional hazards model to adjust for potential confounders.

  • Time to response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Descriptive summaries include Kaplan-Meier plots.

  • Tumor response (complete response [CR] + partial response [PR] + stable disease [SD]) assessed by neurologic exams, radiographic studies, and steroid dose [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    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.
Estimated Enrollment: 60
Study Start Date: March 2003
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (combination chemotherapy)

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.

 Drug: Carboplatin
Given IA
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Etoposide Phosphate
Given IV
Other Name: Etopophos
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm II (combination chemotherapy, sodium thiosulfate)

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.

 Drug: Carboplatin
Given IA
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Etoposide Phosphate
Given IV
Other Name: Etopophos
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Sodium Thiosulfate
Given IV
Other Names:
  • Cyanide Antidote Package
  • Disodium Thiosulfate
  • S-Hydril
  • Sodium Hyposulfate
  • Sodium Thiosulfate Pentahydrate
  • Sodium Thiosulphate
  • Sodothiol
  • Thiosulfate, Sodium, Pentahydrate
  • Thiosulfuric Acid Disodium Salt

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the effect of delayed administration of sodium thiosulfate on the rates of platelet toxicity (ie. 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.

  Eligibility
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075387

Locations
United States, Minnesota
University of Minnesota/Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Matthew A. Hunt    612-624-1452    huntx188@umn.edu   
Principal Investigator: Matthew A. Hunt         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Glen H. Stevens       steveng@ccf.org   
Principal Investigator: Glen H. Stevens         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A. Neuwelt    503-494-5626    neuwelte@ohsu.edu   
Principal Investigator: Edward A. Neuwelt         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
  More Information

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00075387     History of Changes
Other Study ID Numbers: IRB00000922  NCI-2013-00781  MR00041590  CR00023930  eIRB #922  CR00018679  ONC-02019-L  CR00021317  CR00022743  IRB00000922  P30CA069533 
Study First Received: January 9, 2004
Last Updated: May 25, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Etoposide phosphate
Carboplatin
Etoposide
Sodium thiosulfate
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
Antidotes
Protective Agents
Antioxidants
Antitubercular Agents

ClinicalTrials.gov processed this record on September 27, 2016