A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors
A Multi-Center Phase II Study of Selinexor in Treating Recurrent or Refractory Wilms Tumor and Other Pediatric Solid Tumors
1 other identifier
interventional
45
1 country
16
Brief Summary
The purpose of this study is to find out whether selinexor is an effective treatment for people who have a relapsed/refractory Wilms tumor, rhabdoid tumor, MPNST, BCOR-driven sarcoma, or another solid tumor that makes a higher than normal amount of XPO1 or has genetic changes that increase the activity of XP01.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2023
Longer than P75 for phase_2
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2023
CompletedFirst Submitted
Initial submission to the registry
August 2, 2023
CompletedFirst Posted
Study publicly available on registry
August 14, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2029
May 6, 2026
May 1, 2026
6 years
August 2, 2023
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate
To define the antitumor activity of Selinexor in relapsed and refractory Wilms tumor by measuring the Overall Response Rate, defined as Complete Response + Partical Response
6 months following the start of the treatment
Study Arms (5)
Cohort A.1 Wilms Tumor
EXPERIMENTALParticipants will have any type of Wilms tumor or nephroblastoma
Cohort B.1 Rhabdoid Tumor
EXPERIMENTALParticipants will have any Rhabdoid tumor
Cohort C.1 MPNST
EXPERIMENTALParticipants will have progressive, relapsed, unresectable or metastatic MPNST
Cohort D.1 Other Solid Tumor
EXPERIMENTALParticipants must not qualify for Cohorts A, B, or C but have a solid tumor (no hematologic malignancies including lymphoma) for which there is specific evidence that this particular patient's tumor may benefit from selinexor.
Cohort E.1g BCOR driven sarcoma
EXPERIMENTALPatients must have a solid tumor with an activating genomic alteration (e.g. fusion or internal tandem duplication) involving BCOR. Specific examples of qualifying alterations including BCOR-ITD, BCOR-CCNB3,BCOR-MAML3 and ZC3H7B-BCOR;Other potentially qualifying BCOR alterations require approval of study principal investigator; note that loss of function alterations of BCOR would not qualify.
Interventions
This phase II study will initially treat all patients, including adult patients, at the pediatric Selinexor RP2D of 35 mg/m2 (maximum dose 100mg/dose) once weekly using a liquid suspension .
Eligibility Criteria
You may qualify if:
- Age:
- Age ≥ 6 at the time of informed consent
- Age ≥ 2 years to \< 6 years at time of informed consent (Refer to Section 4.3): If PK cohort 1 is open, patients in this age range may enroll onto this cohort. If PK cohort 1 has been completed and deemed sufficient to proceed, then such patients may enroll onto the phase 2.
- Age ≥ 12 months to \< 2 years at time of informed consent (Refer to Section 4.3):
- If PK cohort 2 is open, patients in this age range may enroll onto this cohort. If PK cohort 2 has been completed and deemed sufficient to proceed, then such patients may enroll onto the phase 2.
- Consent: 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.
- Performance: Karnofsky ≥ 60% for patients \> 16 years of age and Lansky ≥ 60 for patients ≤ 16 years of age.
- Diagnosis: Patients must enroll into one of the following cohorts:
- Cohort A: Any type of Wilms tumor or nephroblastoma is eligible for this study provided they meet at least one of these criteria: (1) in their second or greater relapse, (2) refractory or in their first relapse with high risk histology (i.e., any anaplastic or blastemal-type after neoadjuvant chemotherapy), or (3) refractory or in first relapse without high risk histology but after having received chemotherapies other than the initial 4 agents used as current standard of care in the up-front setting for non-high risk cases - specifically vincristine, dactinomycin, doxorubicin, and irinotecan (i.e., any patient who relapses following an initial regimen more intense than EE4A, DD4A, VAD, AVD, or VIVA; for example, those including cyclophosphamide/etoposide - such as Regimen I, M, or MVI - or those additionally including carboplatin - such as Regimens UH-1, UH-2, or UH-3).
- Cohort B: Any Rhabdoid tumor is eligible for this cohort. This includes, but is not limited to, related subtypes of rhabdoid tumors such as atypical teratoid rhabdoid tumors (ATRT), malignant rhabdoid tumors of the kidney (MRTK), malignant rhabdoid tumors of the soft tissue and liver, small cell undifferentiated hepatoblastomas (SCUH), and small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT). Patients must have failed to respond to at least 1 line of systemic therapy prior to enrollment.
- Cohort C: Patients with progressive, relapsed, unresectable or metastatic MPNST, are eligible for this cohort. Patients must have failed to respond to at least 1 line of systemic therapy prior to enrollment.
- Cohort D: Patients must not qualify for Cohorts A, B, or C but have a solid tumor (no hematologic malignancies including lymphoma) for which there is specific evidence that this particular patient's tumor may benefit from selinexor.
- Patients must have failed to respond to at least 1 line of systemic therapy prior to enrollment. Examples of evidence are listed below. All patients in this cohort require approval of study principal investigator and must provide documentation of specific supporting evidence. i. Tumor XPO1 Dependency: Defined as either Darwin OncoTarget demonstrating XPO1 as aberrantly activated or Darwin OncoTreat demonstrating context-specific tumor checkpoint inversion with Selinexor, both of which must be significant at a -log10 (Bonferroni corrected p-value) of 5 or greater. ii. Tumor XPO1 Activation: Defined as the detection of a gain of function mutation in XPO1, specifically E571K. Additionally, detection of elevated transcriptomic or proteomic expression of XPO1 in the tumor via RNAseq or IHC, respectively, would be considered sufficient for treatment.
- iii. Preclinical Tumor Testing: Defined as testing of Selinexor on patient derived cell line, organoid, or xenograft models of the patient's tumor (or other related tumors) performed in a laboratory context and for which, in the investigator's opinion, demonstrates promising activity. Testing may include commercial testing as well as academic laboratory testing.
- Cohort E: Patients must have a solid tumor with an activating genomic alteration (e.g. fusion or internal tandem duplication) involving BCOR. Specific examples of qualifying alterations including BCOR-ITD, BCOR-CCNB3, BCOR-MAML3 and ZC3H7B-BCOR; Other potentially qualifying BCOR alterations require approval of study principal investigator; note that loss of function alterations of BCOR would not qualify.
- +27 more criteria
You may not qualify if:
- Prior Therapy: Has received selinexor or another XPO1 inhibitor previously.
- Infection: Patients who have an uncontrolled infection are not eligible. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable
- Transplants: Patients who have received allogeneic bone marrow transplant are potentially eligible unless they are being actively treated for GvHD. Patients who have had a prior solid organ transplantation are not eligible.
- Compliance: Patients who as a result of serious medical, psychiatric, and/or social situation(s), in the opinion of the investigator, may not be able to comply with supportive care, safety monitoring, or any other key requirements of the study protocols are not eligible.
- Pregnancy and Breast-feeding: Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal.
- Contraception: Males 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 or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Children's Hospital of Los Angeles (Data Collection Only)
Los Angeles, California, 90027, United States
Stanford Medicine Children's Health (Data Collection Only)
Palo Alto, California, 94304, United States
Children's National Hospital (Data Collection Only)
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta (Data Collection and Specimen Analysis)
Atlanta, Georgia, 30322, United States
Ann & Robert H. Lurie Children'S Hospital of Chicag
Chicago, Illinois, 60611, United States
Dana Farber Cancer Institute (Data Collection Only)
Boston, Massachusetts, 02115, United States
Washington University
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited protocol activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities )
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All protocol activites)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited protocol activities)
Rockville Centre, New York, 11553, United States
Cincinnati Children's Hospital Medical Center (Data collection only)
Cincinnati, Ohio, 45229, United States
Cook Children's Health Care System (Data Collection Only)
Fort Worth, Texas, 76104, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Ortiz, MD
Memorial Sloan Kettering Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 2, 2023
First Posted
August 14, 2023
Study Start
August 1, 2023
Primary Completion (Estimated)
August 1, 2029
Study Completion (Estimated)
August 1, 2029
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.