Arsenic Trioxide, Temozolomide, and Radiation Therapy in Treating Patients With Malignant Glioma That Has Been Removed By Surgery
Information source: Northwestern University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Brain and Central Nervous System Tumors
Intervention: arsenic trioxide (Drug); temozolomide (Drug); radiation therapy (Radiation)
Phase: Phase 1/Phase 2
Status: Active, not recruiting
Sponsored by: Northwestern University Official(s) and/or principal investigator(s): Jeffrey Raizer, MD, Principal Investigator, Affiliation: Northwestern University
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.
Clinical Details
Official title: A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapyCollect data on the toxicity of arsenic and temozolomide during radiation therapy Assess serum biomarkers and correlate with tumor tissue
Secondary outcome: Determine progression free survival at 6 and 12 monthsDetermine time to disease progression To determine overall survival To determine radiographic response to study regimen To collect safety data during the radiation therapy phase To evaluate a potential surrogate marker for outcomes
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- 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
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
Locations and Contacts
Hematology-Oncology Associates of Illinois, Chicago, Illinois 60611-2998, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States
Edward Cancer Center, Naperville, Illinois 60540, United States
Additional Information
Starting date: May 2005
Last updated: August 4, 2014
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