Arsenic Trioxide, Temozolomide, and Radiation Therapy in Treating Patients With Malignant Glioma That Has Been Removed By Surgery

NCT ID: NCT00275067

Last Updated: 2020-02-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2021-05-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving arsenic trioxide and temozolomide together with radiation therapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of arsenic trioxide and temozolomide when given together with radiation therapy and to see how well they work in treating patients with malignant glioma that has been removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• 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)

Secondary

• 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 II)
• 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 toxicity.

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation + temozolomide and arsenic trioxide

Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1

Group Type: EXPERIMENTAL

arsenic trioxide

Intervention Type: DRUG

Arsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week

temozolomide

Intervention Type: DRUG

Temozolomide administered orally once per day 1 hour prior to radiation therapy at a dose of 75 mg/m2 x 42 days; at a dose of 200mg/m2 for 5 days every cycle (1 cycle = 28 days) after radiation therapy

radiation therapy

Intervention Type: RADIATION

All patients will receive 5940-6120 cGy of radiation therapy as 28-33 treatments/fractions (180-200 cGy/treatment) depending on whether they receive standard 3-D conformal radiation therapy or intensity modulated radiation therapy.

Interventions

arsenic trioxide

Arsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week

Intervention Type: DRUG

temozolomide

Temozolomide administered orally once per day 1 hour prior to radiation therapy at a dose of 75 mg/m2 x 42 days; at a dose of 200mg/m2 for 5 days every cycle (1 cycle = 28 days) after radiation therapy

Intervention Type: DRUG

radiation therapy

All patients will receive 5940-6120 cGy of radiation therapy as 28-33 treatments/fractions (180-200 cGy/treatment) depending on whether they receive standard 3-D conformal radiation therapy or intensity modulated radiation therapy.

Intervention Type: RADIATION

Other Intervention Names

ATO; TRISENOX; TMZ; Temodar

Eligibility Criteria

Inclusion Criteria

• Evaluable or measurable disease following resection of recurrent tumor is not mandated for entry into the study
• No brain metastases

PATIENT CHARACTERISTICS:

• 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 safety

PRIOR CONCURRENT THERAPY:

• 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 reaction
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cephalon

INDUSTRY

Sponsor Role: collaborator

CTI BioPharma

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Raizer, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Hematology-Oncology Associates of Illinois

Chicago, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Edward Cancer Center

Naperville, Illinois, United States

Countries

United States

Other Identifiers

NU 04C1

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000456504

Identifier Type: REGISTRY

Identifier Source: secondary_id

STU00007792

Identifier Type: OTHER

Identifier Source: secondary_id

NU 04C1

Identifier Type: -

Identifier Source: org_study_id