Clinical trial NCT00077207: Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma
Official title: A Pilot Study Using Carboplatin, Vincristine And Temozolomide For Children ≤ 10 Years With Progressive/Symptomatic Low-Grade Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Tumor
Central Nervous System Tumor
Keywords: untreated childhood cerebellar astrocytoma
untreated childhood visual pathway and hypothalamic glioma
childhood spinal cord neoplasm
childhood oligodendroglioma
childhood low-grade cerebral astrocytoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-11
Enrollment: 66
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin, vincristine, and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells.

PURPOSE: This pilot study is studying giving carboplatin and vincristine together with temozolomide in treating children with progressive and/or symptomatic low-grade glioma.

Detailed description: OBJECTIVES:

Primary

* Determine the feasibility and toxicity of an induction and maintenance regimen comprising carboplatin, vincristine, and temozolomide in children with progressive and/or symptomatic low-grade gliomas.

Secondary

* Determine response rate in patients treated with this regimen.
* Determine 3-year progression-free survival and overall survival of patients treated with this regimen.
* Correlate response and progression-free survival with the genomic profile of tumors in patients treated with this regimen.

OUTLINE: This is a pilot study.

* Induction therapy: Patients receive carboplatin IV over 1 hour on days 1, 8, 15, and 22; vincristine IV on days 1, 8, 15, 22, 29, and 36; and oral temozolomide on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy.
* Maintenance therapy: Patients receive carboplatin and temozolomide as in induction therapy and vincristine IV on days 1, 8, and 15. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed progressive and/or symptomatic low-grade glioma, including any of the following:

  * WHO grade I or II astrocytoma
  * Grade I or II oligodendrogliomas
  * Mixed oligodendrogliomas
  * Gangliogliomas
* Measurable disease
* Progressive and/or symptomatic supratentorial or spinal cord tumors that cannot be removed for anatomical reasons are allowed
* Optic pathway tumors allowed provided there is evidence of progressive disease by MRI and/or symptoms of deteriorating vision, progressive hypothalamic/pituitary dysfunction, or diencephalic syndrome
* Dorsally exophytic brainstem gliomas that were previously resected more than 50% are allowed provided the residual tumor shows progression (with or without symptoms)
* No diffuse brain stem tumors
* No type 1 neurofibromatosis

PATIENT CHARACTERISTICS:

Age

* 10 and under

Performance status

* ECOG 0-2
* Lansky 50-100%

Life expectancy

* Not specified

Hematopoietic

* Hemoglobin ≥ 8.0 gm/dL
* Absolute neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT \< 2.5 times ULN

Renal

* Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
* Creatinine ≤ 0.8 mg/dL (age 5 and under) OR ≤ 1.0 mg/dL (age 6 to10)

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunomodulating agents

Chemotherapy

* No other concurrent anticancer chemotherapy

Endocrine therapy

* Prior corticosteroids allowed
* No concurrent corticosteroids except for the treatment of increased intracranial pressure

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics
* Prior surgery allowed

Other

* No other prior therapy

Primary outcomes:
measure: Short Term Feasibility Success
timeFrame: 24 weeks
measure: Long Term Feasibility Success
timeFrame: 60 weeks
Secondary outcomes:
measure: Number of Participants Who Experienced Toxic Death
timeFrame: Up to 6 years after the start of protocol therapy
measure: Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia.
timeFrame: Up to 18 months of protocol therapy
measure: Percent Probability of Progression-free Survival (PFS)
timeFrame: 3 years
measure: Percentage Probability of Event-free Survival (EFS)
timeFrame: Six years
measure: Total Number of Patients Experiencing a Response
timeFrame: Up to 18 months of protocol therapy
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Childrens Oncology Group
state: Pennsylvania
Study officials:
affiliation: Texas Children's Cancer Center
name: Murali M. Chintagumpala, MD
role: STUDY_CHAIR
References:
citation: Chintagumpala MM, Adesina A, Morriss MC, et al.: A pilot study using carboplatin, vincristine, and temozolomide for children with progressive/symptomatic low-grade glioma: A Children's Oncology Group (COG) study. [Abstract] J Clin Oncol 28 (Suppl 15): A-9539, 2010.