Vinblastine and Carboplatin in Treating Young Patients With Newly Diagnosed or Recurrent Low-Grade Glioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00352495
First received: July 13, 2006
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as vinblastine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vinblastine when given together with carboplatin in treating young patients with newly diagnosed or recurrent low-grade glioma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Neurofibromatosis Type 1
Drug: carboplatin
Drug: vinblastine sulfate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Vinblastine in Combination With Carboplatin for Children With Newly Diagnosed and Recurrent Low-Grade Gliomas

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose and recommended phase II dose of vinblastine in combination with carboplatin [ Time Frame: length of study ] [ Designated as safety issue: Yes ]
  • Acute and dose-limiting toxicities [ Time Frame: length of study ] [ Designated as safety issue: Yes ]
  • Other toxicities [ Time Frame: length of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Radiographic response [ Time Frame: length of study ] [ Designated as safety issue: No ]
  • Changes in diffusion/perfusion imaging [ Time Frame: length of study ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: June 2006
Study Completion Date: March 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vinblastine sulfate and carboplatin
The MTD of vinblastine in combination with a monthly dose of carboplatin will be determined during the first cycle of therapy. Each 4-week cycle will consist of carboplatin once every 4 weeks on day 1. Vinblastine will be given once a week for 3 weeks followed by a one week break. Doses of carboplatin and vinblastine sulfate will be assigned at study enrollment. Patients may receive eleven additional four week cycles, barring tumor progression or unacceptable toxicity. The total duration of therapy will be approximately 48 weeks.
Drug: carboplatin Drug: vinblastine sulfate

Detailed Description:

OBJECTIVES:

Primary

  • Estimate the maximum tolerated dose and recommended phase II dose of vinblastine when given in combination with carboplatin in pediatric patients with newly diagnosed or recurrent low-grade gliomas.
  • Define and describe the acute and dose-limiting toxicities of this regimen.
  • Describe the toxicities associated with repeated courses of the combination chemotherapy regimen and the number of treatment modifications required over the course of treatment.

Secondary

  • Describe the radiographic responses in patients treated with this regimen.
  • Describe changes in diffusion/perfusion imaging during study therapy.

OUTLINE: This is a multicenter, dose-escalation study of vinblastine. Patients are stratified according to amount of prior therapy (heavily pretreated vs less heavily pretreated).

Patients receive carboplatin IV over 30 minutes on day 1 and vinblastine IV on days 1, 8, 15. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vinblastine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* low-grade glioma, including 1 of the following subtypes:

    • Astrocytoma variants

      • Fibrillary, protoplasmic, or mixed
    • Pilocytic astrocytoma, including pilomyxoid variants
    • Pleomorphic xanthoastrocytoma
    • Infantile desmoplastic astrocytoma
    • Ganglioglioma
    • Oligodendroglial tumors
    • Mixed glioma, including oligoastrocytoma NOTE: *Biopsy not required for patients who have visual pathway tumors involving the optic nerves and/or optic radiations (i.e., not isolated to the hypothalamus/chiasm)
  • Biopsy proven focal low-grade gliomas of the brainstem with measurable disease allowed

    • No diffuse, intrinsic brainstem tumors
  • Residual tumor visible on MRI
  • Patients without NF-1 must meet the following criteria:

    • Progressive disease after surgery/biopsy based on clear radiographic or clinical evidence of progression OR gross residual tumor (> 1.5 cm²) after surgery/biopsy that is felt to be a high risk to the patient for neurologic and/or visual impairment if the tumor progresses
    • Visual pathway tumors that are not isolated to the hypothalamus/chiasm and are not biopsied must be a high risk to the patient for neurologic and/or visual impairment
  • Patients with NF-1 must have evidence of radiographic progression on MRI and/or clinical worsening (e.g., worsening of ophthalmologic exam for visual pathway tumors)
  • Meets 1 of the following criteria:

    • Newly diagnosed disease
    • Recurrent disease
  • No ventriculoperitoneal shunt-related ascites

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) OR Lansky PS 50-100% (for patients ≤ 10 years of age)
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³ (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age, as follows:

    • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
    • No greater than 1.0 mg/dL (for patients 6-10 years of age)
    • No greater than 1.2 mg/dL (for patients 11-15 years of age)
    • No greater than 1.5 mg/dL (for patients > 15 years of age)
  • Bilirubin ≤ 1.5 times upper limit of normal
  • ALT ≤ 110 U/L
  • Albumin ≥ 2 g/dL
  • No history of allergy to carboplatin
  • No hyponatremia requiring treatment
  • No uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior therapy except for corticosteroids and surgery (for patients with newly diagnosed disease)
  • Prior chemotherapy and/or radiotherapy in addition to surgery and corticosteroids allowed (for patients with recurrent disease)
  • Prior carboplatin and/or vinblastine allowed if there was no evidence of progressive disease while on therapy and there were no dose reductions due to toxicity (for patients with recurrent disease)
  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered (for patients with recurrent disease)
  • At least 7 days since prior hematopoietic growth factors (for patients with recurrent disease)
  • At least 7 days since prior biological agents (for patients with recurrent disease)
  • At least 9 months since prior external beam radiotherapy or gamma knife therapy that included all target lesions (i.e., there is no restriction if a new lesion arises outside the radiation field or a nonirradiated lesion progresses) and recovered (for patients with recurrent disease)
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents
  • No other concurrent chemotherapy, radiotherapy, immunotherapy, or biological therapy
  • No concurrent corticosteroids for antiemesis
  • Concurrent steroids allowed for tumor edema/increased intracranial pressure provided dose of dexamethasone is stable or decreasing for the past 7 days
  • Concurrent physiologic or stress doses of steroids allowed for endocrine deficiencies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352495

  Show 21 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Regina Jakacki, MD Children's Hospital of Pittsburgh of UPMC
Study Chair: Eric Bouffet, MD, MRCP The Hospital for Sick Children
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00352495     History of Changes
Other Study ID Numbers: ADVL0515, COG-ADVL0515, CDR0000483184
Study First Received: July 13, 2006
Last Updated: February 11, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood low-grade cerebral astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
childhood oligodendroglioma
neurofibromatosis type 1
recurrent childhood visual pathway and hypothalamic glioma
untreated childhood visual pathway and hypothalamic glioma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neurofibromatoses
Neurofibromatosis 1
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Nerve Sheath Neoplasms
Nervous System Diseases
Neurocutaneous Syndromes
Neurodegenerative Diseases
Neurofibroma
Neuromuscular Diseases
Peripheral Nervous System Diseases
Carboplatin
Vinblastine
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014