Treating Patients With High-Grade Glioma With IA Carboplatin-based Chemotherapy, With or Without Sodium Thiosulfate - Full Text View

Sponsor:	OHSU Knight Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00075387

Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and etoposide phosphate, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. Chemoprotective drugs, such as sodium thiosulfate, may protect blood platelets from the side effects of chemotherapy.

PURPOSE: This randomized phase II trial is studying combination chemotherapy and sodium thiosulfate to see how well they work compared to combination chemotherapy alone in treating patients with high-grade glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Thrombocytopenia	Drug: Carboplatin Drug: Cyclophosphamide Drug: Etoposide phosphate Drug: Etoposide Drug: Sodium thiosulfate	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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:

Genetics Home Reference related topics: MYH9-related disorder

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Sodium thiosulfate Etoposide Carboplatin Etoposide phosphate Sodium hyposulfite

U.S. FDA Resources

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:

Protection against severe thrombocytopenia as measured by the number of patients requiring platelet transfusions based on labs obtained weekly during treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tumor response with or without sodium thiosulfate (STS) as measured by radiographic response from the first day of treatment until tumor progression [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Effect of STS on granulocytes and erythrocytes as measured by complete blood count lab values obtained weekly during treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Hearing changes assessed by audiology hearing test every 2 months during treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Quality of life assessed by EORTC QOL before treatment, at 6 months, and at completion of treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	March 2003
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes (or etoposide IV), and carboplatin intra-arterially over 10 minutes on day 1.	Drug: Carboplatin Dose: 400 mg/m2 infused IA. Every 4 weeks for up to 1 year. Drug: Cyclophosphamide Dose: 660 mg/m2 infused IV. Every 4 weeks for up to 1 year. Drug: Etoposide phosphate Dose: 400mg/m2 infused IV. Etoposide may be used instead. Every 4 weeks for up to 1 year. Drug: Etoposide Dose: 400mg/m2 infused IV every 4 weeks for up to 1 year. Etoposide phosphate may be given instead.
Active Comparator: Arm II Patients receive cyclophosphamide, etoposide phosphate or etoposide, and carboplatin as in arm I. At 4 and 8 hours after carboplatin administration, patients receive high-dose sodium thiosulfate IV over 15 minutes.	Drug: Carboplatin Dose: 400 mg/m2 infused IA. Every 4 weeks for up to 1 year. Drug: Cyclophosphamide Dose: 660 mg/m2 infused IV. Every 4 weeks for up to 1 year. Drug: Etoposide phosphate Dose: 400mg/m2 infused IV. Etoposide may be used instead. Every 4 weeks for up to 1 year. Drug: Etoposide Dose: 400mg/m2 infused IV every 4 weeks for up to 1 year. Etoposide phosphate may be given instead. Drug: Sodium thiosulfate Dose: 4 hours after carboplatin = 20gms/m2 Dose: 8 hours after carboplatin = 16gms/m2 Other Name: STS

Arms

Assigned Interventions

Active Comparator: Arm I

Patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes (or etoposide IV), and carboplatin intra-arterially over 10 minutes on day 1.

Drug: Carboplatin

Dose: 400 mg/m2 infused IA. Every 4 weeks for up to 1 year.

Drug: Cyclophosphamide

Dose: 660 mg/m2 infused IV. Every 4 weeks for up to 1 year.

Drug: Etoposide phosphate

Dose: 400mg/m2 infused IV. Etoposide may be used instead. Every 4 weeks for up to 1 year.

Drug: Etoposide

Dose: 400mg/m2 infused IV every 4 weeks for up to 1 year. Etoposide phosphate may be given instead.

Active Comparator: Arm II

Patients receive cyclophosphamide, etoposide phosphate or etoposide, and carboplatin as in arm I. At 4 and 8 hours after carboplatin administration, patients receive high-dose sodium thiosulfate IV over 15 minutes.

Drug: Carboplatin

Dose: 400 mg/m2 infused IA. Every 4 weeks for up to 1 year.

Drug: Cyclophosphamide

Dose: 660 mg/m2 infused IV. Every 4 weeks for up to 1 year.

Drug: Etoposide phosphate

Dose: 400mg/m2 infused IV. Etoposide may be used instead. Every 4 weeks for up to 1 year.

Drug: Etoposide

Dose: 400mg/m2 infused IV every 4 weeks for up to 1 year. Etoposide phosphate may be given instead.

Drug: Sodium thiosulfate

Dose: 4 hours after carboplatin = 20gms/m2

Dose: 8 hours after carboplatin = 16gms/m2

Other Name: STS

Detailed Description:

OBJECTIVES:

Primary

Determine the effect of delayed administration of high-dose sodium thiosulfate on platelet counts in patients with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide, and etoposide or etoposide phosphate.

Secondary

Determine the effect of delayed administration of high-dose sodium thiosulfate on granulocyte and erythrocyte counts in patients treated with this chemotherapy regimen.
Determine the tumor response in patients treated with this chemotherapy regimen with or without delayed high-dose sodium thiosulfate.
Determine hearing changes at higher frequencies in the standard testing range (i.e., 4,000 and 8,000 Hz) and at higher frequencies above standard testing range (i.e., 9,000 and 16,000 Hz) in patients treated with these regimens.
Determine the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology type (glioblastoma multiforme vs other high-grade glioma). Patients are randomized to 1 of 2 treatment arms (Arm 1: no STS or Arm 2: STS).

Arm I: Patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes (or etoposide IV), and carboplatin intra-arterially over 10 minutes on day 1. Beginning on day 3, patients receive filgrastim (G-CSF) subcutaneously once daily for 7-10 days until blood counts recover. Alternatively, one dose of Neulasta (Pegfilgrastim) instead of G-CSF 24-72 hrs after chemotherapy.
Arm II: Patients receive cyclophosphamide, etoposide phosphate or etoposide and carboplatin as in arm 1. At 4 and 8 hours after carboplatin administration, patients receive high-dose sodium thiosulfate IV over 15 minutes. Then, G-CSF as in arm 1. Alternatively, one dose of Neulasta (Pegfilgrastim) instead of G-CSF 24-72 hrs after chemotherapy.

In both arms, treatment repeats every 4 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 6 months during study treatment, and then within 30 days after the final study treatment.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Signed written informed consent form in accordance with institutional guidelines
Histologically confirmed high-grade glioma by needle biopsy, open biopsy, or surgical resection
Age 18 to 75 years
Performance status ECOG 0-2 OR Karnofsky 50-100%
WBC at least 2,500/mm^3
Absolute granulocyte count at least 1,200/mm^3
Platelet count at least 100,000/mm^3
Bilirubin less than 2.0 mg/dL
SGOT/SGPT less than 2.5 times upper limit of normal
Creatinine less than 1.8 mg/dL
Fertile patients must use effective contraception for at least 2 months before and during study participation

EXCLUSION CRITERIA:

Rapidly progressing CNS disease with associated neurological deterioration
Uncontrolled clinically significant confounding medical condition within the past 30 days such as congestive heart failure
Pregnant or lactating, or positive serum HCG.
Contraindications to the study medications

Contacts and Locations

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

Contacts

Contact: Edward A Neuwelt, MD	503-494-5626	neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA	503-494-5626	hedrickn@ohsu.edu

Locations

United States, Minnesota
University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Matthew Hunt, MD 612-626-0975 huntx188@umn.edu
Principal Investigator: Matthew Hunt, MD
United States, Ohio
Good Samaritan Hospital Cancer Treatment Center, Hatton Institute	Recruiting
Cincinnati, Ohio, United States, 45220
Contact: Robert E. Albright, MD 513-936-5370 ralbright@ohcmail.com
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University	Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea 503-494-1080 trials@ohsu.edu
Principal Investigator: Edward A Neuwelt, MD

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Edward A. Neuwelt, MD

OHSU Knight Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00075387 History of Changes
Other Study ID Numbers:	OHSU-922, ONC-02059-L, 922, 7328
Study First Received:	January 9, 2004
Last Updated:	January 11, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by OHSU Knight Cancer Institute:

thrombocytopenia
adult glioblastoma
recurrent adult brain tumor
adult anaplastic astrocytoma
adult mixed glioma

Additional relevant MeSH terms:

Glioma
Nervous System Neoplasms
Thrombocytopenia
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Blood Platelet Disorders
Hematologic Diseases

Cyclophosphamide
Etoposide phosphate
Etoposide
Carboplatin
Sodium thiosulfate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012