A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors

Recruiting now · Phase 2

Conditions studied: Wilms Tumor, Rhabdoid Tumor, Malignant Peripheral Nerve Sheath Tumors, MPNST, Nephroblastoma, XPO1 Gene Mutation, Solid Tumor

In brief

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.

Key facts

Study ID: NCT05985161
Run by: Memorial Sloan Kettering Cancer Center
People needed: 45
Starts: 2023-08-01
Expected to finish: 2029-08-01
Last updated by the study team: 2026-05-06

Who can join

Age: 1 and older. Sex: any. Healthy volunteers: not accepted.

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.
Disease Status: Patients on the phase II portion of the study must have measurable disease whereas patients on the PK cohorts can have either evaluable or measurable disease as measured by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (Version 1.1).
a. Primary Brain Tumors: Patients with primary brain tumors are eligible and must also have measurable disease for the phase II (as well as evaluable or measurable for the PK cohorts), but this can be defined as at least equal or greater than twice the slice thickness in two perpendicular diameters on MRI OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters OR positive CSF cytology alone.
Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and meet minimum washout durations (shown below) from prior therapy.
Anti-cancer agents not known to be myelosuppressive: ≥ 7 days
Anti-cancer and cytotoxic agents known to be myelosuppressive: ≥ 21 days
Immunotherapies (including antibodies, interleukins, interferons, etc.): ≥ 21 days
Adoptive cellular therapies (including modified T cells, vaccines, etc.): ≥ 42 days
Autologous stem cell infusion (boost, no conditioning): ≥ 21 days
Autologous stem cell transplantation (with conditioning): ≥ 42 days
Allogeneic bone marrow transplantation: ≥ 84 days

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.

Where it is running

Children's Hospital of Los Angeles (Data Collection Only) — Los Angeles, California, United States (enrolling)
Stanford Medicine Children's Health (Data Collection Only) — Palo Alto, California, United States (enrolling)
Children's National Hospital (Data Collection Only) — Washington D.C., District of Columbia, United States (enrolling)
Children's Healthcare of Atlanta (Data Collection and Specimen Analysis) — Atlanta, Georgia, United States (enrolling)
Ann & Robert H. Lurie Children'S Hospital of Chicag — Chicago, Illinois, United States (enrolling)
Dana Farber Cancer Institute (Data Collection Only) — Boston, Massachusetts, United States (enrolling)
Washington University — St Louis, Missouri, United States (enrolling)
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (enrolling)
Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (enrolling)
Memorial Sloan Kettering Bergen (Limited protocol activities) — Montvale, New Jersey, United States (enrolling)
Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities ) — Commack, New York, United States (enrolling)
Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (enrolling)
Memorial Sloan Kettering Cancer Center (All protocol activites) — New York, New York, United States (enrolling)
Memorial Sloan Kettering Nassau (Limited protocol activities) — Rockville Centre, New York, United States (enrolling)
Cincinnati Children's Hospital Medical Center (Data collection only) — Cincinnati, Ohio, United States (enrolling)
Cook Children's Health Care System (Data Collection Only) — Fort Worth, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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