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Malignant GliomaPhase 1NCT02323880

Selinexor in Treating Younger Patients With Recurrent or Refractory Solid Tumors or High-Grade Gliomas

A Phase 1 study testing Pharmacological Study and Selinexor in people with Malignant Glioma and Recurrent Brain Neoplasm, run by Children's Oncology Group at 23 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of selinexor in treating younger patients with solid tumors or central nervous system (CNS) tumors that have come back (recurrent) or do not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 12 months to 21 years
What is being tested?
Pharmacological Study and Selinexor
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
23 sitesUnited States
Study dates
30 Oct 2015to 31 Dec 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 months to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must have a body surface area (BSA) >= 0.84 m^2
  • Diagnosis:
  • Part A: Patients with recurrent or refractory solid tumors, including lymphoma and CNS tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
  • Part B: Patients with recurrent or refractory high grade glioma (World Health Organization [WHO] grade III/IV) including disseminated tumors (excluding diffuse intrinsic pontine glioma [DIPG]), not requiring surgical resection; patients must have had histologic verification of malignancy at original diagnosis or relapse
  • Part C: Patients with recurrent or refractory high grade glioma (WHO grade III/IV) and requiring surgical resection (excluding DIPG and disseminated tumors), who in the opinion of treating physicians, are medically stable to receive 2 doses of selinexor (8-10 days of treatment) before undergoing surgery without compromising the success of the procedure; note that if, in the opinion of treating physicians, current symptoms necessitate surgery before 2 doses will be able to be received, surgery should not be delayed to administer selinexor, and the patient would be ineligible for protocol therapy
  • Disease status:
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  • Part A: Patients must have either measurable or evaluable disease
  • Parts B and C: Patients must have measurable disease on imaging
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
  • Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
  • Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
  • 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
  • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
  • External beam radiation therapy (XRT): At least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
  • Stem cell infusion without TBI: No evidence of active graft vs. host disease and at least 56 days must have elapsed after transplant or stem cell infusion
  • Patients must not have received prior exposure to selinexor
  • For patients with solid tumors without known bone marrow involvement:
  • * Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
  • * Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • * Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
  • Patients with known bone marrow metastatic disease will be eligible for study if they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
  • 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:
  • =< 0.6 mg/dL (patients age 1 to < 2 years)
  • =< 0.8 mg/dL (patients age 2 to < 6 years)
  • =< 1 mg/dL (patients age 6 to < 10 years)
  • =< 1.2 mg/dL (patients age 10 to < 13 years)
  • =< 1.4 mg/dL (female patients age >= 13 years)
  • =< 1.5 mg/dL (male patients age 13 to < 16 years)
  • =< 1.7 mg/dL (male patients age >= 16 years)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN = 135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • Serum amylase =< 1.5 x ULN
  • Serum lipase =< 1.5 x ULN
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Patients must be able to swallow tablets whole
  • Part C: Archived paraffin-embedded tissue (20 unstained slides or a tumor block) from a prior resection must be available as a control for correlative studies; if tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Who cannot join

  • Pregnant or breast-feeding women will not be entered on this study, since there is yet no available information regarding human fetal or teratogenic toxicities; based on its mechanism of action and findings in animals, selinexor may cause fetal harm when administered to a pregnant woman; pregnancy tests must be obtained in girls who are post-menarchal; males with female partners of reproductive potential or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control- including a medically accepted barrier method of contraceptive method (e.g., male or female condom) for the entire period in which they are receiving protocol therapy and for at least 1 week following their last dose of study drug; abstinence is an acceptable method of birth control
  • Concomitant medications
  • Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
  • Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
  • Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible
  • Patients who have an uncontrolled infection are not eligible
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  • Patients who have received a prior solid organ transplantation are not eligible
  • Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible
  • Patients with body mass index (BMI) < 3rd percentile for age, as defined by WHO criteria for patients 1-2 years of age and Centers for Disease Control and Prevention (CDC) criteria for patients > 2 years of age, are not eligible
  • Patients with grade 3 ataxia or grade >1 extrapyramidal movement disorder are not eligible
  • Patients with known macular degeneration, uncontrolled glaucoma, or cataracts are not eligible

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase 1 Study of Selinexor (KPT-330), A Selective XPO1 Inhibitor, in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors

This phase I trial studies the side effects and best dose of selinexor in treating younger patients with solid tumors or central nervous system (CNS) tumors that have come back (recurrent) or do not respond to treatment (refractory). Drugs used in chemotherapy, such as selinexor, 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase 2 dose (RP2D) or the maximum tolerated dose (MTD) of the tablet formulation of selinexor in children with recurrent/refractory solid and CNS tumors.

II. To describe the toxicities of selinexor in children with recurrent/refractory solid and CNS tumors.

III. To characterize the pharmacokinetics of the tablet formulation of selinexor in children with recurrent/refractory solid and CNS tumors.

SECONDARY OBJECTIVES:

  1. To determine the antitumor effect of selinexor in a preliminary manner in children with recurrent/refractory solid and CNS tumors.

II. To determine the pharmacodynamic properties of selinexor in children and adolescents with refractory solid tumors in plasma proteins and whole blood ribonucleic acid (RNA).

III. To explore the penetration, pharmacodynamic effects, and biologic effects of selinexor in tumor tissue of patients with recurrent/refractory high-grade gliomas (HGG) requiring resection.

IV. To further assess the toxicity and antitumor effects of selinexor in children with recurrent/refractory HGG in expanded cohorts following dose-escalation by measuring rate of objective radiographic response (medical patients) and rate of progression-free survival (PFS) six months from the start of treatment (surgical patients).

OUTLINE: This is a dose escalation study.

Patients receive selinexor orally (PO) on either a twice weekly (days 1, 3, 8, 10, 15, 17) or once weekly (days 1, 8, 15, and 22) schedule. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Pharmacological Study, Selinexor
Medical subject headings
Glioma, Brain Neoplasms, Central Nervous System Neoplasms, Astrocytoma, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pharmacological StudyOther

    Correlative studies

  • SelinexorDrug

    Also called ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT 330, KPT-330

    Given PO

Study groups in NCT02323880
Study groupRoleWhat they receive
Treatment (selinexor)ExperimentalPatients receive selinexor PO on either a twice weekly (days 1, 3, 8, 10, 15, 17) or once weekly (days 1, 8, 15, and 22) schedule. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Other: Pharmacological Study; Drug: Selinexor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Dose Limiting Toxicities of Selinexor

    The number of toxicity evaluable patients experiencing a dose limiting toxicity at least possibly attributable to selinexor by study part, schema, and dose level.

    Measured: Up to 28 days

  2. Number of Adverse Events of Selinexor

    The number of patients experiencing adverse events at least possibly attributable to selinexor by study part, schema, and dose level.

    Measured: Up to 6 years 11 months

  3. Area Under the Drug Concentration Curve of Selinexor

    The median (min, max) of the area under the drug concentration curve evaluated at 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose on day 1 for Selinexor by study part, schema, and dose level.

    Measured: Up to 2 days

Secondary outcomes (5)

  1. Antitumor Effect of Selinexor

    Number of patients with best response using RECIST 1.1 criteria of partial response (at least a 30% decrease in the sum of the diameters of target lesions) or complete response (disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to <10 mm).

    Measured: Up to 6 years 11 months

  2. Pharmacodynamics of Selinexor

    Median (min,max) ratio of XPO1 mRNA expression after treatment to pre-treatment by study part, schema, and dose

    Measured: Up to 28 days

  3. Pharmacodynamics of Selinexor in High-grade Glioma (HGG) Patients

    Median (min,max) ratio of XPO1 mRNA expression after treatment to pre-treatment by study part, schema, and dose

    Measured: Up to 28 days

  4. Radiographic Response of Selinexor in High-grade Glioma (HGG) Patients

    Number of HGG patients with radiographic response by study part, schema, and dose level.

    Measured: Up to 6 years 11 months

  5. Progression-free Survival of Selinexor in Surgical High-grade Glioma (HGG) Patients

    Number of surgical HGG patients with 6-month progression-free survival using the Response Evaluation Criteria in solid tumors criteria (RECIST v1.1) defining best response of progressive disease including at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study and no prior stable disease, partial response, or complete response.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2014 (estimated)
  2. Study start30 Oct 2015
  3. Primary completion30 Sep 2022
  4. Study completion31 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02323880
Sponsor's protocol ID
ADVL1414
Other IDs
NCI-2014-02410, ADVL1414, ADVL1414, ADVL1414, UM1CA097452
Status last verified
Jan 2025
First submitted
16 Dec 2014
Last updated
14 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Green AL, Minard CG, Liu X, Safgren SL, Pinkney K, Harris L, Link G, DeSisto J, Voss S, Nelson MD, Reid JM, Fox E, Weigel BJ, Glade Bender J. Phase I Trial of Selinexor in Pediatric Recurrent/Refractory Solid and CNS Tumors (ADVL1414): A Children's Oncology Group Phase I Consortium Trial. Clin Cancer Res. 2025 May 1;31(9):1587-1595. doi: 10.1158/1078-0432.CCR-24-2754.

    PubMed 39998852

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pharmacological Study and Selinexor in people with Malignant Glioma and Recurrent Brain Neoplasm, run by Children's Oncology Group at 23 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Dose Limiting Toxicities of Selinexor (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02323880, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.

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