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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00100802
First Posted: January 7, 2005
Last Update Posted: February 27, 2017
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
  Purpose

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.


Condition Intervention Phase
Brain Tumors Central Nervous System Tumors Drug: lomustine Drug: temozolomide Procedure: adjuvant therapy Radiation: radiation therapy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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.


Enrollment: 118
Study Start Date: July 2005
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: lomustine
Capsule
Other Names:
  • Ceenu
  • NSC #79037
Drug: temozolomide
Capsule
Other Names:
  • Temodar
  • NSC # 362856
Procedure: adjuvant therapy Radiation: radiation therapy

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00100802


  Show 150 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Regina Jakacki, MD Children's Hospital of Pittsburgh of UPMC
  More Information

Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00100802     History of Changes
Other Study ID Numbers: 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 )
First Submitted: January 6, 2005
First Posted: January 7, 2005
Results First Submitted: November 18, 2016
Results First Posted: January 13, 2017
Last Update Posted: February 27, 2017
Last Verified: November 2016

Keywords provided by Children's Oncology Group:
childhood high-grade cerebral astrocytoma
childhood spinal cord neoplasm

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Temozolomide
Dacarbazine
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents