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Phase I Study of Combined Radiotherapy and Arsenic Trioxide for the Treatment of Newly Diagnosed Malignant Glioma


Phase 1
18 Years
N/A
Not Enrolling
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

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Trial Information

Phase I Study of Combined Radiotherapy and Arsenic Trioxide for the Treatment of Newly Diagnosed Malignant Glioma


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of ATO in conjunction with radiotherapy and optimum ATO dose for radiosensitization determined by dose-limiting toxicities

Outcome Description:

Results of the safety evaluation will be tabulated and displayed by dose level.

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Samuel Ryu

Investigator Role:

Principal Investigator

Investigator Affiliation:

New Approaches to Brain Tumor Therapy Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03162

NCT ID:

NCT00045565

Start Date:

October 2002

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma
  • Glioma

Name

Location

New Approaches to Brain Tumor Therapy ConsortiumBaltimore, Maryland  21231-1000