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

Primary Purpose

Anaplastic Astrocytoma, Central Nervous System Neoplasm, Glioblastoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Lomustine
Radiation Therapy
Temozolomide
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anaplastic Astrocytoma

Eligibility Criteria

3 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Performance status - Karnofsky 50-100% (for patients > 16 years of age) Performance status - Lansky 50-100% (for patients ≤ 16 years of age) At least 8 weeks Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 (transfusion independent) Hemoglobin ≥ 8 g/dL (transfusions allowed) Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 2.5 times ULN Albumin ≥ 2 g/dL Creatinine ≤ 1.5 times ULN Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal No evidence of dyspnea at rest No exercise intolerance Pulse oximetry ≥ 94% (if determination is clinically indicated) 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 No prior biologic agents No prior chemotherapy Prior corticosteroids allowed No concurrent corticosteroids as an antiemetic Concurrent corticosteroids allowed only for treatment of increased intracranial pressure No concurrent radiotherapy using cobalt-60 See Disease Characteristics No other prior treatment No concurrent phenobarbital or cimetidine No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy

Sites / Locations

  • Children's Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (lomustine, temozolomide, radiation therapy)

Arm Description

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. 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.

Outcomes

Primary Outcome Measures

One Year Overall Survival
Estimated one year survival using the Kaplan-Meier methodology.
Occurrence of Death Attributable to Complications of Protocol Therapy
Number of deaths due to complications of protocol therapy.

Secondary Outcome Measures

Full Information

First Posted
January 6, 2005
Last Updated
January 18, 2023
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00100802
Brief Title
Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
March 21, 2005 (Actual)
Primary Completion Date
September 1, 2012 (Actual)
Study Completion Date
June 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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. 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.
Detailed Description
PRIMARY OBJECTIVES: I. 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. II. Determine the toxicity of this regimen in these patients. III. Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen. IV. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaplastic Astrocytoma, Central Nervous System Neoplasm, Glioblastoma, Gliosarcoma, Spinal Cord Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (lomustine, temozolomide, radiation therapy)
Arm Type
Experimental
Arm Description
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. 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.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Lomustine
Other Intervention Name(s)
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-, Belustin, Belustine, CCNU, Cecenu, CeeNU, Chloroethylcyclohexylnitrosourea, Citostal, Gleostine, Lomeblastin, Lomustinum, Lucostin, Lucostine, N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea, Prava, RB-1509, WR-139017
Intervention Description
Given PO
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
One Year Overall Survival
Description
Estimated one year survival using the Kaplan-Meier methodology.
Time Frame
One year
Title
Occurrence of Death Attributable to Complications of Protocol Therapy
Description
Number of deaths due 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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Performance status - Karnofsky 50-100% (for patients > 16 years of age) Performance status - Lansky 50-100% (for patients ≤ 16 years of age) At least 8 weeks Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 (transfusion independent) Hemoglobin ≥ 8 g/dL (transfusions allowed) Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 2.5 times ULN Albumin ≥ 2 g/dL Creatinine ≤ 1.5 times ULN Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal No evidence of dyspnea at rest No exercise intolerance Pulse oximetry ≥ 94% (if determination is clinically indicated) 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 No prior biologic agents No prior chemotherapy Prior corticosteroids allowed No concurrent corticosteroids as an antiemetic Concurrent corticosteroids allowed only for treatment of increased intracranial pressure No concurrent radiotherapy using cobalt-60 See Disease Characteristics No other prior treatment No concurrent phenobarbital or cimetidine No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Regina I Jakacki
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20607350
Citation
Pollack IF, Hamilton RL, Burger PC, Brat DJ, Rosenblum MK, Murdoch GH, Nikiforova MN, Holmes EJ, Zhou T, Cohen KJ, Jakacki RI; Children's Oncology Group. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group. J Neurooncol. 2010 Sep;99(2):155-63. doi: 10.1007/s11060-010-0297-3. Epub 2010 Jul 4.
Results Reference
background
PubMed Identifier
20589656
Citation
Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Nikiforov YE, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Gilles FH, Yates AJ, Zhou T, Cohen KJ, Finlay JL, Jakacki RI; Children's Oncology Group. Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Dec 1;55(6):1066-71. doi: 10.1002/pbc.22634.
Results Reference
background
PubMed Identifier
20725730
Citation
Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Holmes EJ, Zhou T, Jakacki RI; Children's Oncology Group. IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group. Childs Nerv Syst. 2011 Jan;27(1):87-94. doi: 10.1007/s00381-010-1264-1. Epub 2010 Aug 20.
Results Reference
result

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

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