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Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas

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ClinicalTrials.gov Identifier: NCT00100802
Recruitment Status : Completed
First Posted : January 7, 2005
Results First Posted : January 13, 2017
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE January 6, 2005
First Posted Date  ICMJE January 7, 2005
Results First Submitted Date  ICMJE November 18, 2016
Results First Posted Date  ICMJE January 13, 2017
Last Update Posted Date August 7, 2019
Study Start Date  ICMJE July 2005
Actual Primary Completion Date September 1, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2016)
  • One Year Overall Survival [ Time Frame: One year ]
    Estimated one year survival using the Kaplan-Meier methodology.
  • Occurrence of Death Attributable to Complications of Protocol Therapy [ Time Frame: While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy ]
    Number of deaths due to complications of protocol therapy.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00100802 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
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 Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas
Official Title  ICMJE A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
Brief Summary

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas.

Detailed Description

OBJECTIVES:

  • Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.
  • Determine the toxicity of this regimen in these patients.
  • Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.
  • Correlate polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

  • Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.
  • Maintenance chemotherapy: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50-100 patients will be accrued for this study within 1-1.5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumors
  • Central Nervous System Tumors
Intervention  ICMJE
  • Drug: lomustine
    Capsule
    Other Names:
    • Ceenu
    • NSC #79037
  • Drug: temozolomide
    Capsule
    Other Names:
    • Temodar
    • NSC # 362856
  • Procedure: adjuvant therapy
  • Radiation: radiation therapy
Study Arms  ICMJE Experimental: Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle.
Interventions:
  • Drug: lomustine
  • Drug: temozolomide
  • Procedure: adjuvant therapy
  • Radiation: radiation therapy
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: March 6, 2013)
118
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 30, 2017
Actual Primary Completion Date September 1, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:

    • Anaplastic astrocytoma
    • Glioblastoma multiforme
    • Gliosarcoma
  • Primary spinal cord malignant gliomas allowed
  • No primary brainstem tumors
  • Has undergone surgical resection or biopsy of the tumor within the past 31 days

    • Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries

      • Post-operative MRI not required for patients who undergo biopsy only
  • No evidence of neuraxis dissemination

    • Spine MRI and cerebrospinal fluid cytology required only if clinically indicated

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

  • Karnofsky 50-100% (for patients > 16 years of age)
  • Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)
  • Hemoglobin ≥ 8 g/dL (transfusions allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 2.5 times ULN
  • Albumin ≥ 2 g/dL

Renal

  • Creatinine ≤ 1.5 times ULN OR
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal

Pulmonary

  • No evidence of dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry ≥ 94% (if determination is clinically indicated)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • Able to swallow oral medication
  • Seizures allowed provided they are well controlled with anticonvulsants
  • No hypersensitivity to temozolomide

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic agents

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Prior corticosteroids allowed
  • No concurrent corticosteroids as an antiemetic
  • Concurrent corticosteroids allowed only for treatment of increased intracranial pressure

Radiotherapy

  • No concurrent radiotherapy using cobalt-60

Surgery

  • See Disease Characteristics

Other

  • No other prior treatment
  • No concurrent phenobarbital or cimetidine
  • No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   New Zealand,   Puerto Rico,   Switzerland,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT00100802
Other Study ID Numbers  ICMJE ACNS0423
CDR0000407744 ( Other Identifier: Clinical Trials.gov )
COG-ACNS0423 ( Other Identifier: Children's Oncology Group )
NCI-2012-02645 ( Other Identifier: Registry ID: CTRP (Clinical Trial Reporting Program) )
U10CA098543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Regina Jakacki, MD University of Pittsburgh
PRS Account Children's Oncology Group
Verification Date November 2016

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