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

Glioblastoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00100802
• Other study ID #: ACNS0423
• Secondary ID: NCI-2012-02645AC
• Status: Completed
• Phase: Phase 2
• Start date: March 21, 2005
• Est. completion date: June 30, 2017

Study information

• Verified date: January 2023
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: June 30, 2017
• Est. primary completion date: September 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Astrocytoma
• Central Nervous System Neoplasm
• Central Nervous System Neoplasms
• Glioblastoma
• Gliosarcoma
• Neoplasms
• Nervous System Neoplasms
• Spinal Cord Neoplasm
• Spinal Cord Neoplasms

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lomustine
Given PO

Radiation:
• Radiation Therapy
Undergo radiation therapy

Drug:
• Temozolomide
Given PO

Locations

Country	Name	City	State
United States	Children's Oncology Group	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	One Year Overall Survival	Estimated one year survival using the Kaplan-Meier methodology.	One year
Primary	Occurrence of Death Attributable to Complications of Protocol Therapy	Number of deaths due to complications of protocol therapy.	While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy