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

NCT ID: NCT00100802

Last Updated: 2023-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-21
• Study Completion Date: 2017-06-30

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.

Conditions

Anaplastic Astrocytoma; Central Nervous System Neoplasm; Glioblastoma; Gliosarcoma; Spinal Cord Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (lomustine, temozolomide, radiation therapy)

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Lomustine

Intervention Type: DRUG

Given PO

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Temozolomide

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Lomustine

Given PO

Intervention Type: DRUG

Radiation Therapy

Undergo radiation therapy

Intervention Type: RADIATION

Temozolomide

Given PO

Intervention Type: DRUG

Other Intervention Names

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; Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; 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

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Regina I Jakacki

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20607350 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20589656 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20725730 (View on PubMed)

Other Identifiers

NCI-2012-02645

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACNS0423

Identifier Type: -

Identifier Source: secondary_id

CDR0000407744

Identifier Type: -

Identifier Source: secondary_id

COG-ACNS0423

Identifier Type: -

Identifier Source: secondary_id

ACNS0423

Identifier Type: OTHER

Identifier Source: secondary_id

ACNS0423

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACNS0423

Identifier Type: -

Identifier Source: org_study_id