Clinical trial NCT00352495: Vinblastine and Carboplatin in Treating Young Patients With Newly Diagnosed or Recurrent Low-Grade Glioma
Official title: A Phase I Study of Vinblastine in Combination With Carboplatin for Children With Newly Diagnosed and Recurrent Low-Grade Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Neurofibromatosis Type 1
Keywords: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-07-14
Enrollment: 26
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Maximum tolerated dose and recommended phase II dose of vinblastine in combination with carboplatin
timeFrame: length of study
measure: Acute and dose-limiting toxicities
timeFrame: length of study
measure: Other toxicities
timeFrame: length of study
Secondary outcomes:
measure: Radiographic response
timeFrame: length of study
measure: Changes in diffusion/perfusion imaging
timeFrame: length of study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
state: Alabama
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: University of Pittsburgh
name: Regina Jakacki, MD
role: STUDY_CHAIR
affiliation: The Hospital for Sick Children
name: Eric Bouffet, MD, MRCP
role: STUDY_CHAIR
References:
citation: Jakacki RI, Bouffet E, Adamson PC, Pollack IF, Ingle AM, Voss SD, Blaney SM. A phase 1 study of vinblastine in combination with carboplatin for children with low-grade gliomas: a Children's Oncology Group phase 1 consortium study. Neuro Oncol. 2011 Aug;13(8):910-5. doi: 10.1093/neuonc/nor090. Epub 2011 Jul 15.