Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly Diagnosed Anaplastic Glioma

Radiation Therapy or Radiation Therapy and Temozolomide or Temozolomide Alone in Treating Patients With Newly Diagnosed Anaplastic Glioma
This study is currently recruiting participants.
Verified December 2011 by National Cancer Institute (NCI)

First Received on April 22, 2009.  
Last Updated on June 17, 2012  
History of Changes
Sponsor: North Central Cancer Treatment Group
Collaborators: National Cancer Institute (NCI)
European Organization for Research and Treatment of Cancer – EORTC
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00887146
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving temozolomide alone, radiation therapy alone, or temozolomide together with radiation therapy is more effective in treating anaplastic glioma.

PURPOSE: This randomized phase III trial is comparing giving temozolomide alone, radiation therapy alone, or Temozolomide together to see which works best in treating patients with newly diagnosed anaplastic glioma.

Condition Intervention Phase
Brain and Central Nervous System Tumors Drug: temozolomide
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Phase III Intergroup Study of Radiotherapy Versus Temozolomide Alone Versus Radiotherapy With Concomitant and Adjuvant Temozolomide for Patients With 1p/ 19q Codeleted Anaplastic Glioma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

  • Overall survival [ Designated as safety issue: No ]
  • Time to event (i.e., clinical progression, neurocognitive progression, and radiographic progression) [ Designated as safety issue: No ]

Secondary Outcome Measures:

  • Progression-free survival at 6, 12, and 24 months [ Designated as safety issue: No ]
  • Objective tumor response [ Designated as safety issue: No ]
  • Treatment-related adverse events according to NCI CTCAE v.3 [ Designated as safety issue: Yes ]
  • Interphase fusion of the CEP1 probe and a 19p12 probe to detect the t(1:19) in paraffin-embedded tumor sections by FISH [ Designated as safety issue: No ]
  • Associations between clinical outcomes (survival, progression-free survival, and objective response) and MGMT methylation status [ Designated as safety issue: No ]
  • Additional known prognostic markers including, but not limited to, PTEN, EGFR, EGFRvIII, p53, and any additional markers which are known or are identified during the course of this study that are considered relevant by the study investigators and the … [ Designated as safety issue: No ]

Estimated Enrollment: 488
Study Start Date: October 2009
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions
Active Comparator: Arm I

Patients undergo radiotherapy (RT) 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
Radiation: radiation therapy

Patients undergo radiotherapy
Experimental: Arm II

Patients undergo RT as in arm I and receive oral temozolomide once daily for 6 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant oral temozolomide once daily days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for 6-12 courses in the absence of disease progression and unacceptable toxicity.
Drug: temozolomide

Given orally

Radiation: radiation therapy

Patients undergo radiotherapy
Experimental: Arm III

Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: temozolomide

Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Determine whether there is a survival advantage for patients with newly diagnosed 1p/19q codeleted anaplastic glioma who receive concurrent temozolomide and radiotherapy (RT) followed by adjuvant temozolomide over that observed in patients treated with RT alone (control).

Secondary

  • Determine whether there is a neurocognitive advantage in patients who receive temozolomide alone (Arm III) vs temozolomide with concurrent RT (Arm II) over that observed in patients treated with RT alone (Arm I).
  • Determine whether there is a difference in survival based on t(1;19)(q10,p10) translocation status and MGMT promoter hypermethylation status in these patients.
  • Perform descriptive comparisons of additional secondary outcome endpoints, including time to progression, progression free survival, and the proportion of patients free of progression at 6, 12, and 24 months.
  • Determine the toxicity of RT and concurrent/adjuvant temozolomide in these patients.
  • Determine descriptively whether it is reasonable to delay RT by documenting the time to progression and progression-free survival of patients receiving temozolomide alone.
  • Determine the quality of life and neurocognitive effects in patients treated on this protocol and correlate these results with outcome endpoints.
  • Bank blood products (i.e., plasma, DNA, and buffy coat) and tumor tissue for future scientific investigations.

OUTLINE: This is a multicenter study. Patients are stratified according to cooperative group (EORTC vs North American groups [NCCTG, RTOG, CTSU, and NCIC CTG]), age (≤ 50 years vs > 50 years), and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients undergo radiotherapy (RT) 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo RT as in arm I and receive oral temozolomide once daily on days 1-7 for 6 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant oral temozolomide once daily days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for 6-12 courses in the absence of disease progression and unacceptable toxicity.
  • Arm III: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Patients complete neurocognitive questionnaires (i.e., the Hopkins Verbal Learning test, the Controlled Oral Word Association test from the Multilingual Aphasia Examination, General Mental Ability: Trail Making tests A and B, and the Recall and Recognition of Word List encoded from the HVLT-R test) and quality of life questionnaires (i.e., EORTC QOL-C30 and QOL-BN20) at baseline and periodically during study therapy.

Tumor tissue samples are collected during surgery and analyzed by FISH to detect t(1:19), and for MGMT gene promoter hypermethylation status and additional known prognostic markers, including but not limited to PTEN, EGFR, EGFRvIII, and p53.

After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed 1p/19q codeleted anaplastic glioma

    • Astrocytoma (WHO grade III)
    • Oligodendroglioma
    • Mixed glioma
  • Newly diagnosed disease
  • Willing to provide tissue samples for central pathology
  • Tumor tissue samples available for mandatory central pathology review submission and deletion status determination
  • Must have had surgical diagnosis within the past 3 months

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 3 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during this study and for up to 6 months after the completion of temozolomide treatment
  • Willing to provide tissue samples for translational research purposes
  • Willing and able to complete neurocognitive examination without assistance and quality of life questionnaires with or without assistance
  • No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would preclude patient participation in this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No concomitant serious immunocompromised status (other than that related to concomitant steroids)
  • No active uncontrolled systemic infection or HIV
  • No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No history of myocardial infarction within the past 6 months or congestive heart failure requiring use of concurrent/ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • No recent history of hepatitis infection or at significant risk of reactivation of hepatitis

PRIOR CONCURRENT THERAPY:

  • At least 2 weeks since prior surgery and recovered
  • No prior surgery, radiotherapy or chemotherapy for any CNS neoplasm (hormones, vitamins and growth factors are not considered chemotherapy for the purposes of this study)

    • Prior biopsy and/or resection showing low-grade glioma that has now a biopsy and/or resection showing anaplastic glioma and that has not had any other treatment (radiotherapy or chemotherapy) allowed
  • No concurrent surgical procedures for tumor debulking, other types of chemotherapy, immunotherapy or biologic therapy, or additional stereotactic boost radiotherapy
  • No other concurrent investigational agent that would be considered as a treatment for this cancer
  • No other concurrent specific treatment (other than hormonal therapy) for that cancer in patients with a history of prior malignancy
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887146

Locations
France
Institut Gustave Roussy Recruiting
Villejuif, France, F-94805
Contact: Frederic Dhermain, MD, PhD     33-142-11-4211 ext. 6220     dhermain@igr.fr    
Germany
Universitatsklinikum Heidelberg Recruiting
Heidelberg, Germany, D-69120
Contact: Wolfgang Wick     49-6221-566-703     wolfgang.wick@med.uni-heidelberg.de    
Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3075 EA
Contact: Martin J. van Den Bent, MD     31-10-439-1415     m.vandenbent@erasmusmc.nl    
Sponsors and Collaborators
North Central Cancer Treatment Group
European Organization for Research and Treatment of Cancer – EORTC
Investigators
Study Chair: Kurt A. Jaeckle, MD Mayo Clinic
Principal Investigator: Martin J. van Den Bent, MD Daniel Den Hoed Cancer Center at Erasmus Medical Center
  More Information

Additional Information:

No publications provided

ClinicalTrials.gov Identifier: NCT00887146    
History of Changes
Other Study ID Numbers: CDR0000640442, NCCTG-N0577, EORTC-26081-22086, EudraCT-2008-007295-14
Study First Received: April 22, 2009
Last Updated: June 17, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):

adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma

Additional relevant MeSH terms:

Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2012

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