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

NCT00275067 | Unknown Phase 1 DMC

• 3 other identifiers: NU 04C1CDR0000456504STU00007792
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult anaplastic astrocytoma; adult gliosarcoma; adult anaplastic oligodendroglioma; adult mixed glioma; adult glioblastoma; adult giant cell glioblastoma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (3)

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

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

  Toxicity evaluated prior to each treatment cycle

• Collect data on the toxicity of arsenic and temozolomide during radiation therapy

  Toxicity of this drug combination during radiation therapy will be assessed.

  Toxicity evaluated prior to each treatment cycle

• Assess serum biomarkers and correlate with tumor tissue

  Blood will be drawn at baseline, during radiation therapy, and prior to each cycle of chemotherapy to assess serum biomarkers and correlate with tumor tissue.

  At baseline, during radiation therapy, and prior to each cycle of chemotherapy

Secondary Outcomes (6)

• Determine progression free survival at 6 and 12 months

  At 6 and 12 months after beginning chemotherapy

• Determine time to disease progression

  At 6 and 12 months after beginning chemotherapy

• To determine overall survival

  Every 6 months while on treatment

• To determine radiographic response to study regimen

  Every 6 months while on treatment

• To collect safety data during the radiation therapy phase

  Weekly during radiation therapy

Study Arms (1)

Radiation + temozolomide and arsenic trioxide

EXPERIMENTAL

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

Drug: arsenic trioxide; Drug: temozolomide; Radiation: radiation therapy

Interventions

arsenic trioxide DRUG

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

Also known as: ATO, TRISENOX

Radiation + temozolomide and arsenic trioxide

temozolomide 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

Also known as: TMZ, Temodar

Radiation + temozolomide and arsenic trioxide

radiation therapy 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.

Radiation + temozolomide and arsenic trioxide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• Cephalon: collaborator
• CTI BioPharma: collaborator

Study Sites (3)

Hematology-Oncology Associates of Illinois

Chicago, Illinois, 60611-2998, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Edward Cancer Center

Naperville, Illinois, 60540, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Gliosarcoma; Oligodendroglioma; Glioma; Glioblastoma; Brain Neoplasms

Interventions

Arsenic Trioxide; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Jeffrey Raizer, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 11, 2006
• Study Start: May 1, 2005
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: February 25, 2020

Record last verified: 2020-02

Locations

US (3)