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

NCT ID: NCT00352495

Last Updated: 2014-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2012-03-31

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.

Conditions

Brain and Central Nervous System Tumors; Neurofibromatosis Type 1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

vinblastine sulfate

Intervention Type: DRUG

Interventions

carboplatin

Intervention Type: DRUG

vinblastine sulfate

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Regina Jakacki, MD

Role: STUDY_CHAIR

University of Pittsburgh

Eric Bouffet, MD, MRCP

Role: STUDY_CHAIR

The Hospital for Sick Children

Locations

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, United States

Children's Hospital of Orange County

Orange, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Oregon Health and Science University Cancer Institute

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, 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

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Hospital for Sick Children

Toronto, Ontario, Canada

Hopital Sainte Justine

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 21764821 (View on PubMed)

Other Identifiers

COG-ADVL0515

Identifier Type: -

Identifier Source: secondary_id

CDR0000483184

Identifier Type: -

Identifier Source: secondary_id

ADVL0515

Identifier Type: -

Identifier Source: org_study_id