A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma

April 13, 2024 updated by: National Cancer Institute (NCI)

A Phase 3 Study of Selumetinib (NSC# 748727) or Selumetinib in Combination With Vinblastine for Non-NF1, Non-TSC Patients With Recurrent or Progressive Low-Grade Gliomas (LGGs) Lacking BRAFV600E or IDH1 Mutations

This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of selumetinib sulfate (selumetinib) + vinblastine sulfate (vinblastine) for children with progressive or recurrent low-grade gliomas (LGGs).

II. To determine if selumetinib + vinblastine will lead to improved event-free survival (EFS) outcome compared with selumetinib alone for children with progressive or recurrent LGGs.

SECONDARY OBJECTIVES:

I. To estimate the objective response rates and overall survival associated with treatment with selumetinib + vinblastine versus single-agent selumetinib.

II. To estimate the difference in EFS and response rate between patients with BRAF rearranged LGG and patients with non-BRAF rearranged LGG after treatment with selumetinib + vinblastine versus single-agent selumetinib.

III. To evaluate toxicities associated with selumetinib + vinblastine and single-agent selumetinib for children with progressive or recurrent LGGs.

IV. To compare the quality of life among patients treated with selumetinib + vinblastine and single-agent selumetinib.

V. To examine the vision outcomes among patients with optic pathway gliomas (OPGs) treated with selumetinib + vinblastine and single-agent selumetinib.

EXPLORATORY OBJECTIVE:

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

OUTLINE: This is a dose-escalation feasibility study of vinblastine sulfate in combination with selumetinib, followed by a randomized efficacy study. Patients in the feasibility study are assigned to Arm I, while patients in the efficacy study are randomized to Arm I or Arm II.

ARM I: Patients receive vinblastine sulfate intravenously (IV) over 1 minute or IV infusion on days 1, 8, 15, and 22 and selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days. Patients receive selumetinib and vinblastine for a total duration of 17 cycles followed by 10 additional cycles of selumetinib alone in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection during screening and on study.

ARM II: Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.

After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and annually for years 4-5.

Study Type

Interventional

Enrollment (Estimated)

300

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

  • Canada
      • Quebec, Canada, G1V 4G2
        • Recruiting
        • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
        • Principal Investigator:
          • Bruno Michon
        • Contact:
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • Recruiting
        • University of Alberta Hospital
        • Contact:
        • Principal Investigator:
          • Sarah J. McKillop
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • Recruiting
        • IWK Health Centre
        • Contact:
        • Principal Investigator:
          • Craig Erker
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Recruiting
        • Children's Hospital of Eastern Ontario
        • Contact:
          • Site Public Contact
          • Phone Number: 613-737-7600
        • Principal Investigator:
          • Donna L. Johnston
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Recruiting
        • Centre Hospitalier Universitaire Sainte-Justine
        • Principal Investigator:
          • Monia Marzouki
        • Contact:
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Recruiting
        • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
        • Contact:
        • Principal Investigator:
          • Josee Brossard
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Suspended
        • Children's Hospital of Alabama
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3591
        • Recruiting
        • Arkansas Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 501-364-7373
        • Principal Investigator:
          • David L. Becton
    • California
      • Loma Linda, California, United States, 92354
        • Recruiting
        • Loma Linda University Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 909-558-4050
        • Principal Investigator:
          • Albert Kheradpour
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
        • Contact:
          • Site Public Contact
          • Phone Number: 323-361-4110
        • Principal Investigator:
          • Nathan J. Robison
      • Oakland, California, United States, 94611
        • Recruiting
        • Kaiser Permanente-Oakland
        • Contact:
          • Site Public Contact
          • Phone Number: 877-642-4691
          • Email: Kpoct@kp.org
        • Principal Investigator:
          • Aarati V. Rao
      • Orange, California, United States, 92868
        • Recruiting
        • Children's Hospital of Orange County
        • Contact:
        • Principal Investigator:
          • Elyssa M. Rubin
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado
        • Contact:
        • Principal Investigator:
          • Kathleen M. Dorris
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Connecticut Children's Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 860-545-9981
        • Principal Investigator:
          • Michael S. Isakoff
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Principal Investigator:
          • Asher M. Marks
        • Contact:
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Alfred I duPont Hospital for Children
        • Contact:
        • Principal Investigator:
          • Scott M. Bradfield
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center
        • Principal Investigator:
          • Jeffrey S. Dome
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • University of Florida Health Science Center - Gainesville
        • Contact:
        • Principal Investigator:
          • William B. Slayton
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 954-265-1847
          • Email: OHR@mhs.net
        • Principal Investigator:
          • Iftikhar Hanif
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Nemours Children's Clinic-Jacksonville
        • Contact:
        • Principal Investigator:
          • Scott M. Bradfield
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Arnold Palmer Hospital for Children
        • Contact:
        • Principal Investigator:
          • Amy A. Smith
      • Orlando, Florida, United States, 32827
        • Recruiting
        • Nemours Children's Hospital
        • Contact:
        • Principal Investigator:
          • Scott M. Bradfield
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Children's Healthcare of Atlanta - Egleston
        • Contact:
        • Principal Investigator:
          • Jason R. Fangusaro
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • Saint Luke's Cancer Institute - Boise
        • Principal Investigator:
          • Martha M. Pacheco
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Lurie Children's Hospital-Chicago
        • Contact:
          • Site Public Contact
          • Phone Number: 773-880-4562
        • Principal Investigator:
          • Angela J. Waanders
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Wendy S. Darlington
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois
        • Contact:
          • Site Public Contact
          • Phone Number: 312-355-3046
        • Principal Investigator:
          • Dipti S. Dighe
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Hospital for Children
        • Contact:
          • Site Public Contact
          • Phone Number: 800-248-1199
        • Principal Investigator:
          • Sandeep Batra
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
        • Principal Investigator:
          • David S. Dickens
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Children's Hospital
        • Contact:
        • Principal Investigator:
          • Ashok B. Raj
    • Louisiana
      • New Orleans, Louisiana, United States, 70118
        • Recruiting
        • Children's Hospital New Orleans
        • Contact:
        • Principal Investigator:
          • Lolie C. Yu
    • Maine
      • Scarborough, Maine, United States, 04074
        • Recruiting
        • Maine Children's Cancer Program
        • Contact:
        • Principal Investigator:
          • Stanley Chaleff
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Kenneth J. Cohen
      • Bethesda, Maryland, United States, 20889-5600
        • Recruiting
        • Walter Reed National Military Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 301-319-2100
        • Principal Investigator:
          • Allen I. Stering
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • C S Mott Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
        • Principal Investigator:
          • Andrea T. Franson
      • Royal Oak, Michigan, United States, 48073
        • Recruiting
        • Beaumont Children's Hospital-Royal Oak
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
        • Principal Investigator:
          • Laura K. Gowans
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
        • Principal Investigator:
          • Michael K. Richards
        • Contact:
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota/Masonic Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 612-624-2620
        • Principal Investigator:
          • Christopher L. Moertel
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
        • Principal Investigator:
          • Jonathan D. Schwartz
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • University of Mississippi Medical Center
        • Principal Investigator:
          • Betty L. Herrington
        • Contact:
          • Site Public Contact
          • Phone Number: 601-815-6700
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Contact:
          • Site Public Contact
          • Phone Number: 816-302-6808
          • Email: rryan@cmh.edu
        • Principal Investigator:
          • Keith J. August
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Andrew S. Cluster
      • Saint Louis, Missouri, United States, 63104
        • Recruiting
        • Cardinal Glennon Children's Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 314-268-4000
        • Principal Investigator:
          • William S. Ferguson
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Recruiting
        • Children's Hospital and Medical Center of Omaha
        • Contact:
          • Site Public Contact
          • Phone Number: 402-955-3949
        • Principal Investigator:
          • Jill C. Beck
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
        • Principal Investigator:
          • Jill C. Beck
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Recruiting
        • Morristown Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 973-971-5900
        • Principal Investigator:
          • Kathryn L. Laurie
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 732-235-8675
        • Principal Investigator:
          • Richard A. Drachtman
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Albany Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 518-262-5513
        • Principal Investigator:
          • Lauren R. Weintraub
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Contact:
        • Principal Investigator:
          • Matthew J. Barth
      • New Hyde Park, New York, United States, 11040
        • Recruiting
        • The Steven and Alexandra Cohen Children's Medical Center of New York
        • Contact:
          • Site Public Contact
          • Phone Number: 718-470-3460
        • Principal Investigator:
          • Mark P. Atlas
      • New York, New York, United States, 10065
        • Active, not recruiting
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • Suspended
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Syracuse, New York, United States, 13210
        • Recruiting
        • State University of New York Upstate Medical University
        • Contact:
          • Site Public Contact
          • Phone Number: 315-464-5476
        • Principal Investigator:
          • Philip M. Monteleone
      • Valhalla, New York, United States, 10595
        • Recruiting
        • New York Medical College
        • Contact:
          • Site Public Contact
          • Phone Number: 914-594-3794
        • Principal Investigator:
          • Jessica C. Hochberg
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Carolinas Medical Center/Levine Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-9376
        • Principal Investigator:
          • Joel A. Kaplan
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Jessica M. Sun
        • Contact:
          • Site Public Contact
          • Phone Number: 888-275-3853
      • Greenville, North Carolina, United States, 27834
        • Recruiting
        • East Carolina University
        • Contact:
        • Principal Investigator:
          • Andrea R. Whitfield
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Thomas W. McLean
    • North Dakota
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Akron, Ohio, United States, 44308
        • Recruiting
        • Children's Hospital Medical Center of Akron
        • Contact:
          • Site Public Contact
          • Phone Number: 330-543-3193
        • Principal Investigator:
          • Erin Wright
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Peter M. de Blank
      • Columbus, Ohio, United States, 43205
      • Dayton, Ohio, United States, 45404
        • Recruiting
        • Dayton Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-228-4055
        • Principal Investigator:
          • Mukund G. Dole
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Rene Y. McNall-Knapp
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Linda C. Stork
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • Recruiting
        • Saint Christopher's Hospital for Children
        • Contact:
          • Site Public Contact
          • Phone Number: 215-427-8991
        • Principal Investigator:
          • Gregory E. Halligan
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Children's Hospital of Pittsburgh of UPMC
        • Contact:
        • Principal Investigator:
          • James T. Felker
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Recruiting
        • Prisma Health Richland Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Stuart L. Cramer
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • BI-LO Charities Children's Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Aniket Saha
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Recruiting
        • East Tennessee Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 865-541-8266
        • Principal Investigator:
          • Susan E. Spiller
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University/Ingram Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-811-8480
        • Principal Investigator:
          • Adam J. Esbenshade
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Medical Center of Central Texas
        • Contact:
        • Principal Investigator:
          • Shannon M. Cohn
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Contact:
        • Principal Investigator:
          • Daniel C. Bowers
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 713-798-1354
          • Email: burton@bcm.edu
        • Principal Investigator:
          • Frank Y. Lin
      • San Antonio, Texas, United States, 78207
        • Recruiting
        • Children's Hospital of San Antonio
        • Contact:
        • Principal Investigator:
          • Timothy C. Griffin
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas Health Science Center at San Antonio
        • Contact:
        • Principal Investigator:
          • Shafqat Shah
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Recruiting
        • Primary Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 801-585-5270
        • Principal Investigator:
          • Priya Chan
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Children's Hospital of The King's Daughters
        • Contact:
        • Principal Investigator:
          • Eric J. Lowe
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University/Massey Cancer Center
        • Contact:
        • Principal Investigator:
          • Frances Austin
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 866-987-2000
        • Principal Investigator:
          • Sarah E. Leary
      • Spokane, Washington, United States, 99204
        • Recruiting
        • Providence Sacred Heart Medical Center and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Judy L. Felgenhauer
      • Tacoma, Washington, United States, 98431
        • Recruiting
        • Madigan Army Medical Center
        • Principal Investigator:
          • Melissa A. Forouhar
        • Contact:
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Suspended
        • West Virginia University Healthcare
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Principal Investigator:
          • Kenneth B. De Santes
        • Contact:
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Children's Hospital of Wisconsin
        • Contact:
        • Principal Investigator:
          • Sarah Rumler

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

2 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Feasibility phase: patients must be >= 2 years and =< 21 years of age at the time of enrollment

  • Efficacy phase: patients must be >= 2 years and =< 25 years of age at the time of enrollment

    • All patients > 21 years of age at the time of enrollment must have had initial diagnosis of low-grade glioma by 21 years of age
  • Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment

  • Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1

    • Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC) low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
    • Patients must have progressive or recurrent LGG. Note: Biopsy may be at either initial diagnosis or recurrence

    • Patients must have measurable disease, defined as having a two-dimensional measurable tumor volume of >= 1 cm^2

      • Tumor size will be measured to include both solid and cystic components of the tumor (whether or not tumor is enhancing) + fluid attenuated inversion recovery (FLAIR) signal
    • Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade 1 and II) by the WHO Classification of Tumors of the Central Nervous System - 4th Edition Revised, with the exception of subependymal giant cell astrocytoma
    • Patients with metastatic disease or multiple independent primary LGGs are eligible
  • Patients must be progressive or recurrent after having been treated with at least one prior tumor-directed therapy before enrollment

  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    • Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea);
    • Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent;
    • Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation;
    • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to =< grade 1;
    • MEK inhibitor or vinblastine: Must not have received treatment with a MEK inhibitor or vinblastine within 6 months of study enrollment

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^ 2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):

    • 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 (within 7 days prior to enrollment) (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 (within 7 days prior to enrollment)

    • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
  • Albumin >= 2 g/L (within 7 days prior to enrollment)
  • 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 (within 4 weeks prior to enrollment)
  • Corrected QT interval (QTc interval) =< 450 msec by electrocardiogram (EKG) (within 4 weeks prior to enrollment)
  • Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to enrollment)
  • Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
  • Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
  • 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
  • Stable neurological examination for >= 1 week

  • HYPERTENSION:

    • 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
  • All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment

  • For all patients, an 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

    • Note: If surgical resection or biopsy is performed at the time of progression or recurrence, a post-operative MRI is required
  • 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

Exclusion Criteria:

  • Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following exceptions:

    • Patients must not have had progressive disease while on therapy with vinblastine or a MEK inhibitor;
    • Patients must not have discontinued vinblastine or selumetinib due to toxicity
  • 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 must not have known hypersensitivity to selumetinib, vinblastine, or similar compounds
  • CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
  • 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

  • PRE-EXISTING CONDITIONS (CARDIAC):

    • 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 Heart Association (NYHA) class II-IV prior or current cardiomyopathy
      • Severe valvular heart disease
      • History of atrial fibrillation

  • PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):

    • 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 upper limit of normal (ULN) adjusted by age are not eligible
  • Any multivitamin containing vitamin E must be stopped prior to study enrollment even if it contains less than 100% of the daily recommended dosing for vitamin E

  • Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy, placement of a vascular access device or cerebrospinal 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
  • 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

  • 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
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

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: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Efficacy Phase Arm II (selumetinib)
Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Selumetinib Sulfate
Given PO
Other Names:
  • AZD-6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulphate
  • Koselugo
  • Selumetinib Sulphate
Experimental: Feasibility & Efficacy Phase Arm I (selumetinib, vinblastine)
Patients receive vinblastine sulfate IV over 1 minute or IV infusion on days 1, 8, 15, and 22 and selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days. Patients receive selumetinib and vinblastine for a total duration of 17 cycles followed by 10 additional cycles of selumetinib alone in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Vinblastine Sulfate
Given IV
Other Names:
  • 29060 LE
  • 29060-LE
  • Exal
  • Velban
  • Velbe
  • Velsar
  • VINCALEUKOBLASTINE
Drug: Selumetinib Sulfate
Given PO
Other Names:
  • AZD-6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulfate
  • AZD6244 Hydrogen Sulphate
  • Koselugo
  • Selumetinib Sulphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of selumetinib and vinblastine combination (feasibility)
Time Frame: 1 month post enrollment
The MTD is empirically defined as the highest dose level at which 6 patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic.
1 month post enrollment
Event-free survival (efficacy)
Time Frame: Up to 5 years after enrollment
Will use Kaplan-Meier (KM) methods and stratified log-rank tests to estimate EFS per arm and compare the EFS outcome between the two arms to assess difference in efficacy. EFS is defined as the interval from randomization to the first occurrence of clinical or radiographic disease progression, disease recurrence, subsequent malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up.
Up to 5 years after enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic tumor response rate (efficacy)
Time Frame: Up to 2 years after enrollment
Will summarize the radiologic response rates (complete response [CR] or partial response [PR] per arm and test for a difference between the 2 arms using an exact binomial test. PR is defined as greater than or equal to 50% reduction in target lesion size by bi-dimensional measurement on T2/FLAIR, as compared with the baseline measurements, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 8 weeks. CR must also be sustained for at least 8 weeks and requires complete disappearance of the target lesion on T2/FLAIR imaging (if enhancement had been present, it must have resolved completely); No new lesions, no new T2/FLAIR abnormalities, and no new or increased enhancement; Patients must be off corticosteroids or only on physiological replacement doses; and Patients should be stable or improved clinically.
Up to 2 years after enrollment
Overall survival (OS) (efficacy)
Time Frame: Up to 5 years after enrollment
Will use the KM methods to estimate OS for each treatment arm and use stratified log-rank tests to determine whether there is a difference in OS between the 2 arms. OS is defined as the interval from randomization to death from any cause or to the time of last follow-up for patients who are alive at the time of analysis
Up to 5 years after enrollment
EFS by BRAF Status
Time Frame: Up to 5 years after enrollment
Will use KM methods to estimate the difference in EFS and between patients with BRAF rearranged LGG and patients with non-BRAF rearranged LGG after treatment with selumetinib + vinblastine versus single-agent selumetinib. EFS is defined as the interval from randomization to the first occurrence of clinical or radiographic disease progression, disease recurrence, subsequent malignant neoplasm, or death from any cause. Patients who are event-free will be censored at the time of last follow-up
Up to 5 years after enrollment
Incidence of adverse events (feasibility)
Time Frame: Up to 5 years
Toxicities will be summarized by dose level and by attribution to vinblastine versus selumetinib during the feasibility component.
Up to 5 years
Incidence of adverse events (efficacy)
Time Frame: Up to 5 years
Reported toxicities will be summarized per arm for the efficacy component.
Up to 5 years
Quality of life (QOL)
Time Frame: Baseline to cycle 7 day 1
Will use 2-sample 2-sided t-tests to compare the change from baseline in the PedsQL™ Generic Module Total Scale Score between the two treatment arms at Cycle 7 Day 1 for both patient and parent-proxy report.
Baseline to cycle 7 day 1
Visual outcome comparison
Time Frame: 12 months after enrollment
Will use an exact binomial test to compare the difference in the proportion of subjects in each arm that show improvement in visual acuity per Teller Acuity assessment after 12 months of treatment using a 1-sided test with 10% type 1 error.
12 months after enrollment

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Daniel C Bowers, Children's Oncology Group

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 (Actual)

February 16, 2021

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

October 3, 2020

First Submitted That Met QC Criteria

October 3, 2020

First Posted (Actual)

October 6, 2020

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-07549 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180886 (U.S. NIH Grant/Contract)
  • ACNS1931 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

Clinical Trials on Recurrent WHO Grade 2 Glioma

Clinical Trials on Quality-of-Life Assessment

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe