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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00352495
• Other study ID #: ADVL0515
• Secondary ID: COG-ADVL0515CDR0
• Status: Completed
• Phase: Phase 1
• First received: July 13, 2006
• Last updated: February 11, 2014
• Start date: June 2006
• Est. completion date: March 2012

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type 1

Intervention

Drug:
• carboplatin

• vinblastine sulfate

Locations

Country	Name	City	State
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	St. Louis	Missouri
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose and recommended phase II dose of vinblastine in combination with carboplatin		length of study	Yes
Primary	Acute and dose-limiting toxicities		length of study	Yes
Primary	Other toxicities		length of study	Yes
Secondary	Radiographic response		length of study	No
Secondary	Changes in diffusion/perfusion imaging		length of study	No