Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00100802
Other study ID # ACNS0423
Secondary ID NCI-2012-02645AC
Status Completed
Phase Phase 2
First received
Last updated
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
Health authority
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

Study Design


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
See also
  Status Clinical Trial Phase
Recruiting NCT05664243 - A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma Phase 1/Phase 2
Completed NCT02768389 - Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma Early Phase 1
Recruiting NCT05635734 - Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma Phase 1/Phase 2
Completed NCT03679754 - Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102 Phase 1
Completed NCT01250470 - Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma Phase 1
Terminated NCT03927222 - Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma Phase 2
Recruiting NCT03897491 - PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma Phase 2
Active, not recruiting NCT03587038 - OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma Phase 1
Completed NCT01922076 - Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Phase 1
Recruiting NCT04391062 - Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma Phase 2
Active, not recruiting NCT03661723 - Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma Phase 2
Active, not recruiting NCT02655601 - Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001 Phase 2
Completed NCT02206230 - Trial of Hypofractionated Radiation Therapy for Glioblastoma Phase 2
Completed NCT03493932 - Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade Phase 1
Terminated NCT02709889 - Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT06058988 - Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer Phase 2
Completed NCT03018288 - Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM) Phase 2
Not yet recruiting NCT04552977 - A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Terminated NCT02905643 - Discerning Pseudoprogression vs True Tumor Growth in GBMs