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Arsenic Trioxide Plus Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

Primary Purpose

Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
arsenic trioxide
radiation therapy
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Giant Cell Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment Absolute neutrophil count 1500/mm^3 Platelets 100,000/mm^3 Creatinine =< 1.5 mg/dL Total bilirubin < 2 mg/dl Transaminases < 4 times above the upper limits of the institutional normal Serum potassium > 3.0 and < 5.5mEq/l Magnesium > 1.2 and < 2.5 mEq/l Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits Patients must not be pregnant or breast-feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception; patients who are pregnant or breast-feeding will be excluded because no information on this agent exists with regard to safety for a fetus or breast-feeding infant Patients must have a Karnofsky performance status of >= 60% No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the therapy outlined in this protocol with reasonable safety Patients must have a mini mental score >= 15 Exclusion Criteria: Patients with a prior malignancy; patients with curatively treated carcinoma in situ or basal cell carcinoma of the skin or patients who have been free of disease for >= five years are eligible for this study Patients who are pregnant or breast-feeding; these patients are excluded because no information on this agent exists with regard to safety for a fetus or breast-feeding infant Prior therapy (surgery excluded) for the brain tumor Patients with second-degree heart block Patients who are being treated with Amphotericin B Patients who cannot undergo MRI are not eligible for this study Patients who are currently taking drugs that are known to prolong the QT interval; in order to be eligible patients will need to be off these drugs for >= 5 days prior to starting treatment; patients may not resume these drugs for > 2 weeks after last ATO treatment; if QT prolongation continues after 5 days post drug discontinuation, the patient is not eligible for ATO treatment

Sites / Locations

  • New Approaches to Brain Tumor Therapy Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A

Group B

Arm Description

Patients receive arsenic trioxide IV over 2 hours once weekly for 6 weeks. Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks.

Patients receive arsenic trioxide at a lower dose IV over 2 hours twice weekly for 6 weeks. Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks.

Outcomes

Primary Outcome Measures

Maximum tolerated dose of ATO in conjunction with radiotherapy and optimum ATO dose for radiosensitization determined by dose-limiting toxicities
Results of the safety evaluation will be tabulated and displayed by dose level.
Proportion of patients with serious or life-threatening toxicities using the grading scale of Adverse Events Criteria
Results of the safety evaluation will be tabulated and displayed by dose level. The will be estimated along with 95% confidence intervals.

Secondary Outcome Measures

Duration of survival with this treatment regimen
Non-parametric estimates of survival will be calculated.
Overall event rates (hazards rates)
Will be estimated with 95% confidence intervals.

Full Information

First Posted
September 6, 2002
Last Updated
April 8, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00045565
Brief Title
Arsenic Trioxide Plus Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma
Official Title
Phase I Study of Combined Radiotherapy and Arsenic Trioxide for the Treatment of Newly Diagnosed Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I trial is studying the side effects and best dose of arsenic trioxide and radiation therapy in treating patients with newly diagnosed malignant glioma. Drugs such as arsenic trioxide may stop the growth of malignant glioma by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining arsenic trioxide with radiation therapy may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of Arsenic Trioxide (ATO) when administered on a once a week schedule and a twice a week schedule in conjunction with radiation therapy to patients with newly diagnosed glioblastoma multiforme. II. To determine the toxicity of ATO when it is administered on a once a week schedule and a twice a week schedule in conjunction with radiation therapy in patients with newly diagnosed glioblastoma multiforme. SECONDARY OBJECTIVES: I. To determine the survival of patients with newly diagnosed glioblastoma multiforme receiving ATO when it is administered on a once a week schedule and a twice a week schedule in conjunction with radiation therapy. II. To evaluate the effect of ATO on tumor vasculature by using perfusion MRI. III. To describe the pharmacokinetics of ATO following weekly and twice weekly injection. OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of arsenic trioxide. Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive arsenic trioxide IV over 2 hours once weekly for 6 weeks. Group B: Patients receive arsenic trioxide at a lower dose IV over 2 hours twice weekly for 6 weeks. Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks. In both groups, cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Patients are followed weekly for 4 weeks and then every 2 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Patients receive arsenic trioxide IV over 2 hours once weekly for 6 weeks. Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks.
Arm Title
Group B
Arm Type
Experimental
Arm Description
Patients receive arsenic trioxide at a lower dose IV over 2 hours twice weekly for 6 weeks. Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
arsenic trioxide
Other Intervention Name(s)
Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid Anhydride, AS2O3, Trisenox
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiation therapy
Primary Outcome Measure Information:
Title
Maximum tolerated dose of ATO in conjunction with radiotherapy and optimum ATO dose for radiosensitization determined by dose-limiting toxicities
Description
Results of the safety evaluation will be tabulated and displayed by dose level.
Time Frame
6 weeks
Title
Proportion of patients with serious or life-threatening toxicities using the grading scale of Adverse Events Criteria
Description
Results of the safety evaluation will be tabulated and displayed by dose level. The will be estimated along with 95% confidence intervals.
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Duration of survival with this treatment regimen
Description
Non-parametric estimates of survival will be calculated.
Time Frame
Up to 6 years
Title
Overall event rates (hazards rates)
Description
Will be estimated with 95% confidence intervals.
Time Frame
Up to 6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment Absolute neutrophil count 1500/mm^3 Platelets 100,000/mm^3 Creatinine =< 1.5 mg/dL Total bilirubin < 2 mg/dl Transaminases < 4 times above the upper limits of the institutional normal Serum potassium > 3.0 and < 5.5mEq/l Magnesium > 1.2 and < 2.5 mEq/l Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits Patients must not be pregnant or breast-feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception; patients who are pregnant or breast-feeding will be excluded because no information on this agent exists with regard to safety for a fetus or breast-feeding infant Patients must have a Karnofsky performance status of >= 60% No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the therapy outlined in this protocol with reasonable safety Patients must have a mini mental score >= 15 Exclusion Criteria: Patients with a prior malignancy; patients with curatively treated carcinoma in situ or basal cell carcinoma of the skin or patients who have been free of disease for >= five years are eligible for this study Patients who are pregnant or breast-feeding; these patients are excluded because no information on this agent exists with regard to safety for a fetus or breast-feeding infant Prior therapy (surgery excluded) for the brain tumor Patients with second-degree heart block Patients who are being treated with Amphotericin B Patients who cannot undergo MRI are not eligible for this study Patients who are currently taking drugs that are known to prolong the QT interval; in order to be eligible patients will need to be off these drugs for >= 5 days prior to starting treatment; patients may not resume these drugs for > 2 weeks after last ATO treatment; if QT prolongation continues after 5 days post drug discontinuation, the patient is not eligible for ATO treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel Ryu
Organizational Affiliation
New Approaches to Brain Tumor Therapy Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
New Approaches to Brain Tumor Therapy Consortium
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-1000
Country
United States

12. IPD Sharing Statement

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Arsenic Trioxide Plus Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

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