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

NCT02323880 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: ADVL1414NCI-2014-02410UM1CA097452
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 23

Brief 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). 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.

Conditions

Malignant Glioma; Recurrent Brain Neoplasm; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Primary Central Nervous System Neoplasm; WHO Grade 3 Glioma

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 28 days

• 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.

  Up to 6 years 11 months

• 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.

  Up to 2 days

Secondary Outcomes (5)

• Antitumor Effect of Selinexor

  Up to 6 years 11 months

• Pharmacodynamics of Selinexor

  Up to 28 days

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

  Up to 28 days

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

  Up to 6 years 11 months

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

  Up to 6 months

Study Arms (1)

Treatment (selinexor)

EXPERIMENTAL

Patients 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.

Other: Pharmacological Study; Drug: Selinexor

Interventions

Pharmacological Study OTHER

Correlative studies

Treatment (selinexor)

Selinexor DRUG

Given PO

Also known as: ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT 330, KPT-330, KPT330, Nexpovio, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330, Xpovio

Treatment (selinexor)

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (23)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 39998852 DERIVED

MeSH Terms

Conditions

Glioma; Brain Neoplasms; Central Nervous System Neoplasms; Astrocytoma; Lymphoma

Interventions

selinexor

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

16264470064

Study Officials

• Julia Glade-Bender

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2014
• First Posted: December 24, 2014
• Study Start: October 30, 2015
• Primary Completion: September 30, 2022
• Study Completion: December 31, 2024
• Last Updated: January 14, 2025
• Results First Posted: January 2, 2024

Record last verified: 2025-01

Locations

US (23)