A Study Comparing Two Carboplatin Containing Regimens for Children and Young Adults With Previously Untreated Low Grade Glioma

NCT ID: NCT02455245

Last Updated: 2024-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-31

Study Completion Date

2025-11-30

Brief Summary

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This study is trying to learn and understand if the chemotherapy drug called carboplatin works as well as the standard therapy. The standard therapy for Low Grade Glioma (LGG) in children and young adults is using a combination of carboplatin and vincristine. Studies in children have shown that the use of carboplatin alone has promise of being just as effective for treating LGG as standard therapy. Additionally, this study will try to understand if treatment with carboplatin alone is associated with an improved quality of life for LGG patients and their families.

Detailed Description

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Low grade gliomas are the most common central nervous system (CNS) tumors in the pediatric population. They consist of a heterogeneous group of tumors that are classified as World Health Organization (WHO) grade I or II. This includes astrocytic, oligodendroglial, neuronal and mixed glial- neuronal tumors. The clinical behavior of these tumors varies according to location and histology. The cerebellum is the most common location for low grade gliomas, but they can also arise in the cerebrum, deep midline structures such as the hypothalamus, optic pathway and, less frequently, in the brainstem.

Although the etiology of most childhood LGG is unknown, patients with Neurofibromatosis type 1 (NF-1) are one rare group predisposed to developing CNS tumors. NF-1 is an inherited disorder that affects the nervous system, eyes and skin. In addition, children are at an increased risk for developing optic pathway and hypothalamic low grade gliomas. Fifteen to-20% of NF-1 patients will develop these tumors, and they account for up to 70% of the tumors seen in this location. In half of patients with NF-1 and an optic pathway tumor, the patients are not symptomatic and the mass is found incidentally. Many optic gliomas in NF-1 patients follow an indolent course and stabilize without intervention. Patients are most commonly treated when there is deterioration in their vision or a symptomatic increase in the tumor size. Although the event free survival (EFS) has been reported to be similar between NF1 and non-NF1 patients, overall survival is higher in NF1 patients.

Location, as it affects the extent of surgical resection, plays a key role in the prognosis of all patients with low grade gliomas. Complete surgical resection offers a 90% survival rate at 10 years with often no need for adjuvant chemotherapy or radiation. Unfortunately, a gross total resection is not always possible due to the location of the tumor and its proximity to vital structures in the brain. In patients with an incomplete resection, the 10 year EFS is up to 74% with radiation treatment. However, toxicity from radiation, especially in young children, is significant and includes neurocognitive delays, endocrinopathies, secondary malignancy, ototoxicity and vasculopathy. Therefore, most experts agree that the standard of care in young children is to treat low grade gliomas that require adjuvant therapy after surgical resection/biopsy, or whose tumors are not surgically resectable with chemotherapy first, in order to delay or avoid radiation. This is especially true in children with NF-1, where the risk of a secondary malignancy after radiation therapy can be as high as 50% in the lifetime of the child.

Conditions

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Low Grade Glioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Carboplatine and Vincristine

Induction: 10 weeks of Carboplatin and Vincristine therapy. Carboplatin 175 mg/m2 give an an IV infusion weeks 1, 2, 3, 4, 7, 8, 9, 10. Vincristine 1.5mg/m2 (0.05 mg/kg if child less than 12 kg) (maximum dose 2.0 mg) give as an IV bolus infusion on weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

Maintenance: Maintenance consists of 8, 6-week cycles of chemotherapy. It begins week 12 of Induction or when peripheral counts recover with ANC \>1,000/µL and platelet count \>100,000/µL. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.

Carboplatin 175 mg/m2 as an IV continuous infusion over 60 minutes on Week 1, 2, 3, 4 of each cycle. Vincristine 1.5 mg/m2 (0.05 mg/ kg for children \<12 kg) (maximum dose 2.0 mg) IV bolus infusion on Week 1, 2, 3 of each cycle.

Group Type ACTIVE_COMPARATOR

Carboplatin and Vincristine

Intervention Type DRUG

Carboplatin 175 mg/m2 IV infusion Vincristine 1.5mg/m2 IV

Carboplatin

Intervention Type DRUG

Carboplatin 560 mg/m2 (or 19 mg/kg for children weighing less than 12 kg) IV

Carboplatin alone

Carboplatin is given once every four weeks, Each 4-week period is considered a cycle. Regimen B will last for 13 cycles which is equivalent to one year (52 weeks).

Carboplatin 560 mg/m2 (or 19 mg/kg for children weighing less than 12 kg) IV over 1 hour every 4 weeks

Group Type EXPERIMENTAL

Carboplatin and Vincristine

Intervention Type DRUG

Carboplatin 175 mg/m2 IV infusion Vincristine 1.5mg/m2 IV

Interventions

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Carboplatin and Vincristine

Carboplatin 175 mg/m2 IV infusion Vincristine 1.5mg/m2 IV

Intervention Type DRUG

Carboplatin

Carboplatin 560 mg/m2 (or 19 mg/kg for children weighing less than 12 kg) IV

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Tumor Diagnosis: Low grade gliomas
* Patients must be less than 21 years of age at study entry.
* Central nervous system tumor. Patients with primary spinal cord lesions. Patients with metastatic disease are also allowed.
* No previous therapy for the tumor with the exception of corticosteroids and surgery.
* Performance status:Karnofsky Performance Scale (KPS for \> 16 yrs of age) or Lansky Performance Score (LPS for ≤ 16 years of age) ≥ 50 assessed within two weeks prior to registration
* Seizure disorder should be well controlled.
* Normal organ and marrow function
* 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 prior to enrollment.
* 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.
* Tissue blocks or slides must be sent. If tissue is unavailable, the study chair must be notified prior to enrollment.

Exclusion Criteria

* Patients who are receiving any other investigational or chemotherapeutic agents will be excluded.
* Patients with known inability to return for follow-up visits or obtain follow-up studies required to assess for toxicity to therapy.
* Patients with Subepenydmal Giant Cell Astrocytomas are excluded. Patients with intrinsic brainstem tumors of the pons will be excluded from the study.
* 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.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alicia Lenzen

OTHER

Sponsor Role lead

Responsible Party

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Alicia Lenzen

Attending

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Alicia Lenzen, MD

Role: PRINCIPAL_INVESTIGATOR

Attending

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Rady Children's Hospital

San Diego, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Orlando Health, Inc.

Orlando, Florida, United States

Site Status

Ann & Robert H. Lurie Children's Hosptial of Chicago

Chicago, Illinois, United States

Site Status

St. Vincent Peyton Manning Children's Hospital

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan, C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Saint Louis University at SSM Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Duke University Medical School

Durham, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

American Family Children's Hospital

Madison, Wisconsin, United States

Site Status

Medical College of Wiscosin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Gururangan S, Cavazos CM, Ashley D, Herndon JE 2nd, Bruggers CS, Moghrabi A, Scarcella DL, Watral M, Tourt-Uhlig S, Reardon D, Friedman HS. Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol. 2002 Jul 1;20(13):2951-8. doi: 10.1200/JCO.2002.12.008.

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Sharif S, Ferner R, Birch JM, Gillespie JE, Gattamaneni HR, Baser ME, Evans DG. Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol. 2006 Jun 1;24(16):2570-5. doi: 10.1200/JCO.2005.03.8349.

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Petronio J, Edwards MS, Prados M, Freyberger S, Rabbitt J, Silver P, Levin VA. Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg. 1991 May;74(5):701-8. doi: 10.3171/jns.1991.74.5.0701.

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Other Identifiers

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LGG 14C03

Identifier Type: -

Identifier Source: org_study_id

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