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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00077207
First received: February 10, 2004
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Brain Tumor
Central Nervous System Tumor
Drug: carboplatin
Drug: temozolomide
Drug: vincristine sulfate

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study Using Carboplatin, Vincristine And Temozolomide For Children ≤ 10 Years With Progressive/Symptomatic Low-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Feasibility of delivering this chemotherapy regimen at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Feasibility defined as the ability to administer induction plus one maintenance cycle

  • Feasibility defined as the ability to administer induction plus four maintenance cycles [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
    This is the long-term feasibility endpoint. Defined as the ability to administer induction + four maintenance cycles (i.e., to start the fifth maintenance cycle) within 60 weeks


Secondary Outcome Measures:
  • Occurrence of toxic death [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Grade 3 or 4 thrombocytopenia and/or neutropenia [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    Grade 3 or 4 thrombocytopenia and/or neutropenia that results in more than a 3 week delay in instituting the next cycle of chemotherapy despite protocol-directed reduction of up to 25% in Carboplatin and/or Temozolomide during the first 60 weeks of therapy

  • Progression-free survival (PFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Preliminary assessments of treatment efficacy will be based on response to induction therapy, 3-year progression-free survival (PFS)

  • Event-free survival (EFS) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Preliminary assessments of treatment efficacy will be based on response to induction therapy, 3-year event-free survival(EFS)

  • Response rate categorized as complete response, partial response, stable disease, or progressive disease [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 66
Study Start Date: July 2004
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (carboplatin, vincristine sulfate, temozolomide)
Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) 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 (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.
Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC #241240
Drug: temozolomide
Given orally
Other Names:
  • Temodar
  • NSC# 362856
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574

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

Ages Eligible for Study:   up to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077207

  Show 104 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Murali M. Chintagumpala, MD Texas Children's Cancer Center
  More Information

Additional Information:
Publications:
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.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00077207     History of Changes
Other Study ID Numbers: ACNS0223, CDR0000350005, COG-ACNS0223, NCI-2012-02572
Study First Received: February 10, 2004
Last Updated: October 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood cerebellar astrocytoma
untreated childhood visual pathway and hypothalamic glioma
childhood spinal cord neoplasm
childhood oligodendroglioma
childhood low-grade cerebral astrocytoma

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vincristine
Temozolomide
Dacarbazine
Carboplatin
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on April 21, 2014