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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00275067
Recruitment Status : Active, not recruiting
First Posted : January 11, 2006
Last Update Posted : February 20, 2019
Sponsor:
Collaborators:
Cephalon
CTI BioPharma
Information provided by (Responsible Party):
Northwestern University

Tracking Information
First Submitted Date  ICMJE January 10, 2006
First Posted Date  ICMJE January 11, 2006
Last Update Posted Date February 20, 2019
Study Start Date  ICMJE May 2005
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2010)
  • Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy [ Time Frame: Toxicity evaluated prior to each treatment cycle ]
    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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00275067 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2010)
  • Determine progression free survival at 6 and 12 months [ Time Frame: At 6 and 12 months after beginning chemotherapy ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Arsenic Trioxide, Temozolomide, and Radiation Therapy in Treating Patients With Malignant Glioma That Has Been Removed By Surgery
Official Title  ICMJE A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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
Interventions:
  • Drug: arsenic trioxide
  • Drug: temozolomide
  • Radiation: radiation therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2010)
50
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00275067
Other Study ID Numbers  ICMJE NU 04C1
NU 04C1 ( Other Identifier: Northwestern University )
CDR0000456504 ( Registry Identifier: PDQ )
STU00007792 ( Other Identifier: Northwestern University IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE
  • Cephalon
  • CTI BioPharma
Investigators  ICMJE
Principal Investigator: Jeffrey Raizer, MD Northwestern University
PRS Account Northwestern University
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP