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A Phase I Study of Vinblastine in Combination With Carboplatin for Children With Newly Diagnosed and Recurrent Low-Grade Gliomas

Phase 1
21 Years
Not Enrolling
Brain and Central Nervous System Tumors, Neurofibromatosis Type 1

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Trial Information

A Phase I Study of Vinblastine in Combination With Carboplatin for Children With Newly Diagnosed and Recurrent Low-Grade Gliomas



- 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.


- 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

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.

Inclusion Criteria


- 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

- 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

- 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


- 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


- 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

- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and recommended phase II dose of vinblastine in combination with carboplatin

Safety Issue:


Principal Investigator

Regina Jakacki, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital of Pittsburgh of UPMC


United States: Federal Government

Study ID:




Start Date:

June 2006

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Neurofibromatosis Type 1
  • 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
  • Glioma
  • Nervous System Neoplasms
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Central Nervous System Neoplasms



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Children's Hospital of Orange County Orange, California  92668
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Baylor University Medical Center - Houston Houston, Texas  77030-2399
Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana  46202-5289
C.S. Mott Children's Hospital at University of Michigan Medical Center Ann Arbor, Michigan  48109-0286
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis St. Louis, Missouri  63110
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center New York, New York  10032
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham Birmingham, Alabama  35294
Oregon Health and Science University Cancer Institute Portland, Oregon  97239-3098