Summary

Eligibility
for people ages 2-21 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

This phase III trial studies how well selumetinib works in treating patients with low-grade glioma. Selumetinib is a drug that works by blocking a protein (a basic building block of the human body) that lets tumor cells grow without stopping. Drugs used in chemotherapy, such as carboplatin and vincristine, 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. This trial studies if selumetinib works as well as carboplatin and vincristine for getting rid of or shrinking low-grade gliomas and stopping them from coming back.

Official Title

A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)

Details

PRIMARY OBJECTIVE:

  1. To demonstrate that the efficacy of treatment with selumetinib as measured by event-free survival (EFS) is non-inferior compared to treatment with carboplatin/vincristine (CV) in previously-untreated low-grade glioma (LGG) not associated with BRAFV600E mutations or systemic neurofibromatosis type 1 (NF1).

SECONDARY OBJECTIVES:

  1. To estimate tumor response rates to each regimen of chemotherapy. II. To evaluate visual acuity (VA) outcomes utilizing Teller Acuity Cards (TAC) and HOTV letter acuity testing in previously-untreated optic pathway gliomas (OPGs).

III. To describe the improvement in motor function as measured by the Vineland Scale in children with previously-untreated LGG that have motor deficits at enrollment.

IV. To estimate the difference in EFS and tumor response rate between BRAF rearranged and non-BRAF rearranged patients treated on each chemotherapy regimen.

  1. To prospectively evaluate the quality of life of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.

VI. To prospectively evaluate the cognitive, social, emotional, and behavioral functioning of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.

EXPLORATORY OBJECTIVE:

  1. To obtain paired blood and tumor specimens for future biology studies, including studies to correlate genomic drivers to response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

INDUCTION: Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and then annually for years 4-10.

Keywords

Astrocytoma Low Grade Glioma Glioma Carboplatin Vincristine Quality-of-Life Assessment Selumetinib Sulfate Vincristine Sulfate

Eligibility

You can join if…

Open to people ages 2-21

  • Patients must have a body surface area (BSA) of >= 0.5 m2 at enrollment

  • Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
  • Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
  • Patients must have two-dimensional measurable tumor >= 1 cm2 to be eligible

  • Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
  • Patients with metastatic disease or multiple independent primary LGG are eligible
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m2 OR a serum creatinine based on age/gender as follows:

  • Age: Maximum Serum Creatinine (mg/dL)
  • 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
  • 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
  • 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
  • 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
  • >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
  • Albumin >= 2 g/dL
  • Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram
  • Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG)
  • Absolute neutrophil count >= 1,000/uL (unsupported)
  • Platelets >= 100,000/uL (unsupported)
  • Hemoglobin >= 8 g/dL (may be supported)
  • Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
  • Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications)
  • Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
  • Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
  • For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have the ability to swallow whole capsules

You CAN'T join if...

  • Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
  • Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
  • Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
  • Patients may not be receiving any other investigational agents
  • Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
  • Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
  • Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants are not eligible
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
  • Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
  • Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
  • Symptomatic heart failure
  • New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
  • Severe valvular heart disease
  • History of atrial fibrillation
  • Current or past history of central serous retinopathy
  • Current or past history of retinal vein occlusion or retinal detachment
  • Patients with uncontrolled glaucoma
  • If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
  • Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
  • Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
  • Note: Patients must have healed from any prior surgery
  • Patients who have an uncontrolled infection are not eligible

Locations

  • UCSF Medical Center-Mission Bay accepting new patients
    San Francisco California 94158 United States
  • Kaiser Permanente-Oakland accepting new patients
    Oakland California 94611 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Cancer Institute (NCI)
ID
NCT04166409
Phase
Phase 3
Study Type
Interventional
Last Updated