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

March 23, 2018 updated by: Natasha Pillay Smiley

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

160

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Phoenix Children's Hospital
        • Contact:
          • Amy Rosenfield, MD
        • Contact:
    • California
      • San Diego, California, United States, 92123
        • Not yet recruiting
        • Rady Children's Hospital
        • Contact:
          • John Crawford, MD
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
          • Asher M Marks, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Recruiting
        • St. Vincent Peyton Manning Children's Hospital
        • Contact:
          • Jessica Goodman, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • The Johns Hopkins Hospital
        • Contact:
          • Ken Cohen, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
        • Contact:
          • Anne E Bendel, MD
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43205
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • American Family Children's Hospital
        • Contact:
          • Neha Patel, MD
          • Phone Number: 608-263-6200
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: 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.
Drug: Vincristine
Drug: Carboplatin
EXPERIMENTAL: 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
Drug: Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants who experience improved quality of life as assessed by a Quality of Life questionnaire.
Time Frame: week-6, week-12, month-6, month-12
week-6, week-12, month-6, month-12
Tumor response rate of each regimen, assessed by magnetic resonance imaging (MRI)
Time Frame: 3 years
3 years
Number of participants who experience toxicity on each regimen
Time Frame: 3 years
3 years
Number of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations that have an association with clinical outcomes.
Time Frame: 3 years
3 years
Number of aberrations found through whole exome and ribonucleic acid (RNA) sequencing that coordinate with a clinical outcome.
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Natasha Pillay Smiley

Investigators

  • Principal Investigator: Natasha Pillay Smiley, DO, Attending

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (ANTICIPATED)

April 1, 2020

Study Completion (ANTICIPATED)

April 1, 2021

Study Registration Dates

First Submitted

April 13, 2015

First Submitted That Met QC Criteria

May 22, 2015

First Posted (ESTIMATE)

May 27, 2015

Study Record Updates

Last Update Posted (ACTUAL)

March 26, 2018

Last Update Submitted That Met QC Criteria

March 23, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LGG 14C03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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