Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma

Brain Tumor Clinical Trial

Official title:

A Pilot Study Using Carboplatin, Vincristine And Temozolomide For Children ≤ 10 Years With Progressive/Symptomatic Low-Grade Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00077207
• Other study ID #: ACNS0223
• Secondary ID: CDR0000350005COG
• Status: Completed
• Phase: N/A
• Start date: July 2004
• Est. completion date: December 2013

Study information

• Verified date: April 2018
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 2013
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Tumor
• Central Nervous System Neoplasms
• Central Nervous System Tumor
• Glioma
• Nervous System Neoplasms

Intervention

Drug:
• carboplatin
Given IV
• temozolomide
Given orally
• vincristine sulfate
Given IV

Locations

Country	Name	City	State
United States	Childrens 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 (1)

Chintagumpala M, Eckel SP, Krailo M, Morris M, Adesina A, Packer R, Lau C, Gajjar A. A pilot study using carboplatin, vincristine, and temozolomide in children with progressive/symptomatic low-grade glioma: a Children's Oncology Group study†. Neuro Oncol. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Short Term Feasibility Success	Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage.; Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure.	24 weeks
Primary	Long Term Feasibility Success	Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage.; If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success.	60 weeks
Secondary	Number of Participants Who Experienced Toxic Death	Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin.	Up to 6 years after the start of protocol therapy
Secondary	Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia.	Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy.	Up to 18 months of protocol therapy
Secondary	Percent Probability of Progression-free Survival (PFS)	Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment.	3 years
Secondary	Percentage Probability of Event-free Survival (EFS)	Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment.	Six years
Secondary	Total Number of Patients Experiencing a Response	Response as complete response, partial response, stable disease, or progressive disease using three-dimensional imaging measurements (preferable) or two-dimensional imaging measurements, as well as the response in the context of multiple lesions or disseminated disease.	Up to 18 months of protocol therapy