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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00100802
First received: January 6, 2005
Last updated: July 31, 2014
Last verified: July 2014
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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: Time to death from any cause, assessed up to 1 year after enrollment ] [ Designated as safety issue: No ]
  • The occurrence of death attributable to complications of protocol therapy [ Time Frame: While receiving protocol therapy or within 30 days of the termination of protocol therapy ] [ Designated as safety issue: Yes ]
    Cumulative incidence of toxic death primarily attributable to complications of treatment


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, Maintneance, 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/m 2/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

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
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
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: NCT00100802

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

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00100802     History of Changes
Other Study ID Numbers: ACNS0423, CDR0000407744, COG-ACNS0423, NCI-2012-02645, U10CA98543
Study First Received: January 6, 2005
Last Updated: July 31, 2014
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on October 23, 2014