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A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas

Phase 1/Phase 2
18 Years
Open (Enrolling)
Brain and Central Nervous System Tumors

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Trial Information

A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas



- Determine the maximum tolerated dose (MTD) of arsenic trioxide and temozolomide when
combined with radiotherapy in patients with resected supratentorial malignant glioma.
(Phase I)

- Determine the toxicity of this regimen in these patients. (Phase I)


- Determine the 6- and 12-month progression-free survival of patients treated with this
regimen once an MTD is reached. (Phase II)

- Determine the radiographic response for patients treated with the above regimen. (Phase

- Determine the safety of this regimen in these patients. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of arsenic trioxide and temozolomide
followed by a phase II study.

- Phase I: Patients undergo radiotherapy once daily 5 days a week and receive oral
temozolomide once daily for approximately 6½ weeks. Patients also receive arsenic
trioxide IV over 1-4 hours once daily, 5 days a week in week 1 and then twice a week in
weeks 2-7. Beginning within 3-5 weeks after completion of radiotherapy, patients
receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats
every 28 days for up to 1 year in the absence of disease progression and unacceptable

Cohorts of 3-6 patients receive escalating doses of arsenic trioxide and temozolomide until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.

- Phase II: Patients undergo radiotherapy and receive arsenic trioxide and temozolomide
as in phase I at the MTD. Patients then receive temozolomide as in phase I for up to 1
year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for the phase I portion of this
study. A total of 25 patients will be accrued for the phase II portion of this study.

Inclusion Criteria


- Histologically confirmed supratentorial malignant glioma of 1 of the following types:

- Glioblastoma multiforme

- Gliosarcoma

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed gliomas

- Anaplastic gliomas not otherwise specified

- Has undergone surgical resection of tumor

- Patients with biopsy only are eligible

- Evaluable or measurable disease following resection of recurrent tumor is not
mandated for entry into the study

- No brain metastases


- Karnofsky performance status 60-100%

- Life expectancy > 3 months

- WBC > 3,000/mm^3

- Absolute neutrophil count > 2,000/mm^3

- Platelet count > 100,000/mm^3

- Hemoglobin > 10 g/dL (eligibility level for hemoglobin may be reached by transfusion)

- Creatinine ≤ 1.5 mg/dL

- Bilirubin ≤ 2 mg/dL

- Transaminases ≤ 2 times the upper limit of normal

- Serum potassium* > 4.0 mEq/dL

- Serum magnesium* > 1.8 mg/dL NOTE: *If these serum electrolytes are below the
specified limits on the baseline laboratory tests, supplemental electrolytes should
be administered to bring the serum concentrations to these levels before
administering arsenic trioxide

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- No second-degree heart block

- QT interval ≤ 460 msec

- No other malignancy within the past 3 years except curatively treated carcinoma in
situ or basal cell carcinoma of the skin

- Patients who cannot undergo MRI are not eligible for this study

- No other serious concurrent infection or other medical illness that would jeopardize
the ability of the patient to receive the therapy in this protocol with reasonable


- See Disease Characteristics

- Patients must have recovered from the effects of surgery prior to the start of
treatment (10-14 days minimum) and be maintained on a stable corticosteroid regimen
for 5 days

- Concurrent glucocorticoid therapy allowed at the smallest effective dose

- Patients must be on non-enzyme-inducing anti-convulsants to minimize any drug

- No prior radiation therapy, chemotherapy, immunotherapy, therapy with biologic agents
(including immunotoxins, immunoconjugates, antisense agents, peptide receptor
antagonists, interferons, interleukins, tumor-infiltrating lymphocytes,
lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their
brain tumor

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy

Outcome Description:

Escalating doses of study drug until dose limiting toxicities are observed.

Outcome Time Frame:

Toxicity evaluated prior to each treatment cycle

Safety Issue:


Principal Investigator

Jeffrey Raizer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University


United States: Federal Government

Study ID:

NU 04C1



Start Date:

May 2005

Completion Date:

May 2015

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult anaplastic astrocytoma
  • adult gliosarcoma
  • adult anaplastic oligodendroglioma
  • adult mixed glioma
  • adult glioblastoma
  • adult giant cell glioblastoma
  • recurrent adult brain tumor
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Hematology-Oncology Associates of Illinois Chicago, Illinois  60611-2998
Edward Cancer Center Naperville, Illinois  60540