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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cephalon
CTI BioPharma
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00275067
First received: January 10, 2006
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: arsenic trioxide
Drug: temozolomide
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy [ Time Frame: Toxicity evaluated prior to each treatment cycle ] [ Designated as safety issue: Yes ]
    Escalating doses of study drug until dose limiting toxicities are observed.

  • Collect data on the toxicity of arsenic and temozolomide during radiation therapy [ Time Frame: Toxicity evaluated prior to each treatment cycle ] [ Designated as safety issue: Yes ]
    Toxicity of this drug combination during radiation therapy will be assessed.

  • Assess serum biomarkers and correlate with tumor tissue [ Time Frame: At baseline, during radiation therapy, and prior to each cycle of chemotherapy ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Determine progression free survival at 6 and 12 months [ Time Frame: At 6 and 12 months after beginning chemotherapy ] [ Designated as safety issue: No ]
    Patients will undergo an MRI and neurological evaluation every 6 months while on chemotherapy.

  • Determine time to disease progression [ Time Frame: At 6 and 12 months after beginning chemotherapy ] [ Designated as safety issue: No ]
    Disease status will be assessed by MRI and neurological examination every 6 months until disease progression.

  • To determine overall survival [ Time Frame: Every 6 months while on treatment ] [ Designated as safety issue: No ]
    Survival status will be evaluated every 6 months while on treatment.

  • To determine radiographic response to study regimen [ Time Frame: Every 6 months while on treatment ] [ Designated as safety issue: No ]
    Radiographic response will be assessed by MRI every 6 months while on treatment

  • To collect safety data during the radiation therapy phase [ Time Frame: Weekly during radiation therapy ] [ Designated as safety issue: Yes ]
    EKG's will be done once per week and labs twice per week during radiation therapy phase to evaluate safety data.

  • To evaluate a potential surrogate marker for outcomes [ Time Frame: At baseline, before and after radiation therapy, and every 2 cycles during chemotherapy ] [ Designated as safety issue: No ]
    Blood will be drawn to analyze methylation patterns as a surrogate marker for outcomes at baseline, before and after radiation therapy, and every 2 cycles during chemotherapy.


Estimated Enrollment: 50
Study Start Date: May 2005
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: arsenic trioxide
Arsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week
Other Names:
  • ATO
  • TRISENOX
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
Other Names:
  • TMZ
  • Temodar
Radiation: 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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275067

Locations
United States, Illinois
Hematology-Oncology Associates of Illinois
Chicago, Illinois, United States, 60611-2998
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Edward Cancer Center
Naperville, Illinois, United States, 60540
Sponsors and Collaborators
Northwestern University
Cephalon
CTI BioPharma
Investigators
Principal Investigator: Jeffrey Raizer, MD Northwestern University
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00275067     History of Changes
Other Study ID Numbers: NU 04C1, NU 04C1, CDR0000456504, STU00007792
Study First Received: January 10, 2006
Last Updated: August 4, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Northwestern University:
adult anaplastic astrocytoma
adult gliosarcoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult glioblastoma
adult giant cell glioblastoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Arsenic trioxide
Temozolomide
Dacarbazine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014