Clinical trial NCT00100802: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anaplastic Astrocytoma
Central Nervous System Neoplasm
Glioblastoma
Gliosarcoma
Spinal Cord Neoplasm
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-01-07
Enrollment: 118
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: One Year Overall Survival
timeFrame: One year
measure: Occurrence of Death Attributable to Complications of Protocol Therapy
timeFrame: While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Oncology Group
state: Pennsylvania
Study officials:
affiliation: Children's Oncology Group
name: Regina I Jakacki
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.