Carboplatin with or without Vincristine Sulfate in Treating Younger Patients with Previously Untreated Low Grade Glioma

Status: Active

Description

This randomized, phase III trial compares carboplatin with or without vincristine sulfate in treating younger patients with previously untreated low grade glioma. Drugs used in chemotherapy, such as carboplatin and vincristine sulfate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether carboplatin is more effective with or without vincristine sulfate in treating low grade glioma.

Eligibility Criteria

Inclusion Criteria

  • Patients who are newly OR previously diagnosed with low grade glioma (LGG), who have not been treated with any modality besides surgery or corticosteroids; untreated astrocytomas or other eligible tumors (with the exception of subependymal giant cell astrocytoma) interpreted as low grade (World Health Organization [WHO] grade I and II), will be eligible for the study as below (4th edition WHO classification of central nervous system [CNS] tumors); if it is clinically suspected that the previously untreated progressive low grade astrocytoma has evolved to a higher grade tumor, it is recommended a biopsy be performed; patients with metastatic disease are allowed on study
  • Glial tumors (including patients with leptomeningeal disease) * Astrocytic tumors ** Low-grade astrocytoma (variants: fibrillary, protoplasmic gemistocytic, mixed, not otherwise specified [NOS]) ** Pilocytic astrocytoma ** Pleomorphic xanthoastrocytomas ** Infantile desmoplastic astrocytoma ** Pilomyxoid astrocytoma * Low-grade oligodendroglioma * Low-grade oligoastrocytoma
  • Neuronal tumors * Ganglioglioma (excluding tumors with anaplastic astrocytic components) * Infantile desmoplastic ganglioglioma
  • Optic pathway tumors, including chiasmatic-hypothalamic, tumor without histologic confirmation; patients with chiasmatic lesions with or without contiguous extension of tumor into other regions of the visual pathways demonstrated on contrast magnetic resonance imaging (MRI) will be eligible for study without histopathologic confirmation with or without NF-1
  • Low grade glioma NOS
  • All NF-1 patients with a LGG are eligible for Stratum 2, with or without histologic confirmation, provided they have never previously received adjuvant therapy with the exception of surgery
  • Tumors of all locations in the central nervous system, with appropriate histology, are eligible for study; however, patients with intrinsic brainstem tumors of the pons will be excluded from the study; patients with primary spinal cord lesions are allowed; patients with metastatic disease are also allowed
  • Treatment must be scheduled to commence within 14 working days after registration and may not begin prior to registration.
  • Patients must have received no previous therapy for the tumor with the exception of corticosteroids and surgery; patients with a gross total resection will not be eligible
  • Karnofsky performance scale ([KPS] for > 16 yrs of age) or Lansky performance score ([LPS] for =< 16 years of age) >= 50
  • Patients with a seizure disorder should be well controlled
  • Absolute neutrophil count >= 1000/ mm^3 (unsupported) and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Platelets >= 100,000/ mm^3 (unsupported) and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Hemoglobin >= 8 g/dL (with or without packed red blood cell [PRBC] transfusion) and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Total bilirubin < 1.5 times upper limit of normal for age and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Albumin >= 2 g/dL and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3.0 times institutional upper limit of normal for age and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3.0 times institutional upper limit of normal for age and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Serum creatinine =< 1.5 times upper limit of institutional normal for age, or and documented within 14 days prior to registration and within 14 days prior to the start of treatment
  • Creatinine clearance or nuclear glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age as follows: =< 5 years: maximum serum creatinine 0.8 mg/dL 5 years < age =< 10 years: maximum serum creatinine 1 mg/dL 10 years < age =< 15 years: maximum serum creatinine 1.2 mg/dL > 15 years: maximum serum creatinine 1.5 mg/dL
  • Lab values must also be verified, meeting eligibility criteria, within 14 days prior to starting treatment. If treatment is planned > 14 days after lab values were obtained for registration, labs must be repeated
  • Female patients of childbearing potential must not be pregnant or breast-feeding; female patients who have menstruated and are of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration
  • Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 6 months after the last drug administration
  • Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent/assent document; informed consent/assent must be signed prior to registration on this study
  • All subjects must have MRI scans of the brain within 28 days prior to registration; an MRI of the spine should be performed if clinically indicated
  • Tissue availability must be verified prior to registration; if tissue is unavailable, the study chair must be notified prior to enrollment; tissue blocks or slides will be sent to Dana Farber Cancer Institute; NF-1 patients, as well as those with optic pathway, including chiasmatic-hypothalamic lesions (with or without NF-1) are not required to have a biopsy; all others are, if deemed safe by their clinical team * Note: All patients who have tissue available must also have a pre-treatment blood sample collected

Exclusion Criteria

  • Patients who are receiving any other investigational or chemotherapeutic agents will be excluded; please contact the study principal investigator (PI) if a patient has received an investigational or chemotherapeutic agent in the past
  • Patients with known inability to return for follow-up visits or obtain follow-up studies required to assess for toxicity to therapy will be excluded
  • Patients with subependymal giant cell astrocytomas are excluded; patients with intrinsic brain stem tumors of the pons will be excluded from the study
  • Patents with history of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to platinum based chemotherapy
  • Patients with uncontrolled inter-current illness are excluded
  • Females who are pregnant or breast feeding are excluded since there are unknown teratogenic effects of these agents
  • The study is open to all participants regardless of gender or ethnicity; efforts will be made to extend the accrual to a representative population; if differences in outcome that correlate to gender, racial, or ethnic identity are noted, accrual may be expanded or additional studies may be performed to investigate those differences more fully
  • All therapy should be dispensed at the primary institution; we encourage all imaging studies to be reviewed and reported by the primary institution; laboratory studies may be performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory of the investigator’s choice

Locations & Contacts

Arizona

Phoenix
Phoenix Childrens Hospital
Status: Active
Contact: Cynthia Wetmore
Phone: 602-933-0920
Email: Cwetmore@phoenixchildrens.com

California

San Diego
Rady Children's Hospital - San Diego
Status: Active
Contact: John Ross Crawford
Phone: 858-966-5811
Email: jrcrawford@ucsd.edu

Connecticut

New Haven
Yale University
Status: Active
Contact: Asher Michael Marks
Phone: 203-785-4640
Email: asher.marks@yale.edu

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: Active
Contact: Natasha Pillay Smiley
Phone: 312-227-4874
Email: npillaysmiley@luriechildrens.org

Indiana

Indianapolis
Saint Vincent Hospital and Health Care Center
Status: Active
Contact: Jessica Farrell Goodman
Phone: 317-338-4673
Email: jfgoodma@stvincent.org

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Contact: Mariko Sato
Phone: 319-353-6393
Email: mariko-sato@uiowa.edu

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Kenneth J. Cohen
Phone: 410-955-5055
Email: kcohen@jhmi.edu

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Active
Contact: Karen Denise Wright
Phone: 617-632-4244
Email: KarenD_Wright@dfci.harvard.edu

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: Active
Contact: Carl Johannes Koschmann
Email: ckoschma@umich.edu

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: Active
Contact: Anne Elizabeth Bendel
Phone: 612-813-5940
Email: anne.bendel@childrensmn.org

Missouri

Saint Louis
Cardinal Glennon Children's Medical Center
Status: Active
Contact: Mohamed Shebl Abdel Baki
Phone: 314-577-5638
Email: abdelbakims@slu.edu
Saint Louis Children's Hospital
Status: Active
Contact: Karen M. Gauvain
Email: gauvaink@wustl.edu

New York

Albany
Albany Medical Center
Status: Active
Contact: Lauren R. Weintraub
Email: weintrl@mail.amc.edu

North Carolina

Durham
Duke University Medical Center
Status: In review
Contact: David Michael Ashley
Phone: 919-684-5301
Email: david.ashley@duke.edu

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: Active
Contact: Sarah Zieber Rush
Email: srush@chmca.org
Columbus
Nationwide Children's Hospital
Status: Active
Contact: Diana Soraya Osorio
Phone: 614-722-4087
Email: Diana.Osorio@nationwidechildrens.org
Dayton
Dayton Children's Hospital
Status: Active
Contact: Ayman Aly El-Sheikh
Email: elsheikha@childrensdayton.org

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Neha J. Patel
Phone: 608-263-6200
Email: npatel@pediatrics.wisc.edu
Milwaukee
Children's Hospital of Wisconsin
Status: Active
Contact: Jeffrey Alan Knipstein
Email: jknipstein@mcw.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) in patients with previously untreated low grade glioma (LGG) among patients with and without neurofibromatosis type 1 (NF-1) utilizing two carboplatin containing regimens; carboplatin/vincristine (vincristine sulfate) (standard of care [SOC]) versus single agent carboplatin (research).

SECONDARY OBJECTIVES:

I. To compare the quality of life of children and young adults with LGG treated with carboplatin versus carboplatin and vincristine.

II. To estimate tumor response rates to each regimen of chemotherapy.

III. To determine toxicity of each regimen.

IV. To assess the associations that B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations have on clinical outcomes.

V. To assess aberrations found through whole exome and ribonucleic acid (RNA) sequencing and correlate with clinical outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment regimens.

REGIMEN A:

INDUCTION: Patients receive carboplatin intravenously (IV) over 60 minutes on weeks 1, 2, 3, 4, 7, 8, 9, and 10. Patients also receive vincristine sulfate IV on weeks 1-10. Treatment continues for 10 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning week 12 of induction therapy or when peripheral counts recover with absolute neutrophil count > 1,000/uL and platelet count > 100,000/uL, patients receive carboplatin IV over 60 minutes on weeks 1-4, and vincristine sulfate IV on weeks 1-3. Treatment repeats every 6 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

REGIMEN B: Patients receive carboplatin IV over 1 hour. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, and 9 months, at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, and 7 years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Lurie Children's Hospital-Chicago

Principal Investigator
Natasha Pillay Smiley

Trial IDs

Primary ID LCH 14C03
Secondary IDs NCI-2015-01146, LGG-14C03, 2014-15932
Clinicaltrials.gov ID NCT02455245