RECRUITING

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

Conditions

Wilms Tumor Rhabdoid Tumor Malignant Peripheral Nerve Sheath Tumors MPNST Nephroblastoma XPO1 Gene Mutation Solid Tumor XPO1 Selinexor Memorial Sloan Kettering Cancer Center 22-393

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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, or another solid tumor that makes a higher than normal amount of XPO1 or has genetic changes that increase the activity of XP01.

Official Title

A Multi-Center Phase II Study of Selinexor in Treating Recurrent or Refractory Wilms Tumor and Other Pediatric Solid Tumors

Quick Facts

Study Start:2023-08-01

Study Completion:2029-08-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05985161

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.

Ages Eligible for Study:12 Months

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age: 1. Age ≥ 6 at the time of informed consent 2. 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. 3. Age ≥ 12 months to \< 2 years at time of informed consent (Refer to Section 4.3): * 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: 1. 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). 2. 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 3. 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. 4. 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. * 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). * 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. 1. Anti-cancer agents not known to be myelosuppressive: ≥ 7 days 2. Anti-cancer and cytotoxic agents known to be myelosuppressive: ≥ 21 days 3. Immunotherapies (including antibodies, interleukins, interferons, etc.): ≥ 21 days 4. Adoptive cellular therapies (including modified T cells, vaccines, etc.): ≥ 42 days 5. Autologous stem cell infusion (boost, no conditioning): ≥ 21 days 6. Autologous stem cell transplantation (with conditioning): ≥ 42 days 7. Allogeneic bone marrow transplantation: ≥ 84 days 8. Focal external beam radiation (e.g., limited sites of disease): ≥ 14 days 9. Substantial external beam radiation (e.g. whole lung or abdomen): ≥ 42 days 10. Radiopharmaceutical therapy (e.g., radiolabeled antibody or MIBG): ≥ 42 days * Hepatic Function: Adequate function (within 14 days prior to C1D1), defined as: 1. Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome, who must have a total bilirubin of \<3 × ULN) 2. Alanine aminotransferase (ALT) \< 3 × ULN 3. Serum albumin ≥ 2 g/dL * Renal Function: Adequate function (within 14 days prior to C1D1) defined as a GFR 1. Nuclear radioisotope 2. 24 hr urine creatinine clearance 3. Serum cystatin c 4. Serum creatinine using the Schwartz formula for estimating creatinine clearance (Schwartz et al. J Peds, 106:522, 1985) * Hematologic Function: Adequate function (within 14 days prior to C1D1), defined as: 1. Absolute neutrophil count (ANC) ≥ 1000/mm3 2. Platelet count ≥ 100,000/mm3 3. Note: patients may not receive platelet transfusions nor hematopoietic growth factor support, including granulocyte-colony stimulating factor (e.g. filgrastim) and platelet stimulators (e.g. romiplostim) for at least 7 days prior to demonstrating adequate hematologic function.	* 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.

Inclusion Criteria

Exclusion Criteria

* Age:
1. Age ≥ 6 at the time of informed consent
2. 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.
3. Age ≥ 12 months to \< 2 years at time of informed consent (Refer to Section 4.3):
* 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:
1. 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).
2. 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
3. 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.
4. 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.
* 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).
* 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.
1. Anti-cancer agents not known to be myelosuppressive: ≥ 7 days
2. Anti-cancer and cytotoxic agents known to be myelosuppressive: ≥ 21 days
3. Immunotherapies (including antibodies, interleukins, interferons, etc.): ≥ 21 days
4. Adoptive cellular therapies (including modified T cells, vaccines, etc.): ≥ 42 days
5. Autologous stem cell infusion (boost, no conditioning): ≥ 21 days
6. Autologous stem cell transplantation (with conditioning): ≥ 42 days
7. Allogeneic bone marrow transplantation: ≥ 84 days
8. Focal external beam radiation (e.g., limited sites of disease): ≥ 14 days
9. Substantial external beam radiation (e.g. whole lung or abdomen): ≥ 42 days
10. Radiopharmaceutical therapy (e.g., radiolabeled antibody or MIBG): ≥ 42 days
* Hepatic Function: Adequate function (within 14 days prior to C1D1), defined as:
1. Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome, who must have a total bilirubin of \<3 × ULN)
2. Alanine aminotransferase (ALT) \< 3 × ULN
3. Serum albumin ≥ 2 g/dL
* Renal Function: Adequate function (within 14 days prior to C1D1) defined as a GFR
1. Nuclear radioisotope
2. 24 hr urine creatinine clearance
3. Serum cystatin c
4. Serum creatinine using the Schwartz formula for estimating creatinine clearance (Schwartz et al. J Peds, 106:522, 1985)
* Hematologic Function: Adequate function (within 14 days prior to C1D1), defined as:
1. Absolute neutrophil count (ANC) ≥ 1000/mm3
2. Platelet count ≥ 100,000/mm3
3. Note: patients may not receive platelet transfusions nor hematopoietic growth factor support, including granulocyte-colony stimulating factor (e.g. filgrastim) and platelet stimulators (e.g. romiplostim) for at least 7 days prior to demonstrating adequate hematologic function.

* 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.

Contacts and Locations

Study Contact

Michael Ortiz, MD

CONTACT

1-833-MSK-KIDS

ortizm2@mskcc.org

Julia Glade Bender, MD

CONTACT

1-833-MSK-KIDS

Principal Investigator

Michael Ortiz, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Children's Hospital of Los Angeles (Data Collection Only)

Los Angeles, California, 90027

United States

Children's Healthcare of Atlanta (Data Collection and Specimen Analysis)

Atlanta, Georgia, 30322

United States

Dana Farber Cancer Institute (Data Collection Only)

Boston, Massachusetts, 02115

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

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Michael Ortiz, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

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 Registration Dates

Study Start Date2023-08-01

Study Completion Date2029-08-01

Study Record Updates

Study Start Date2023-08-01

Study Completion Date2029-08-01

Terms related to this study

Keywords Provided by Researchers

Wilms Tumor
Rhabdoid Tumor
Malignant Peripheral Nerve Sheath Tumors
MPNST
Nephroblastoma
XPO1
Selinexor
Memorial Sloan Kettering Cancer Center
22-393
Solid Tumor

Additional Relevant MeSH Terms

Wilms Tumor
Rhabdoid Tumor
Malignant Peripheral Nerve Sheath Tumors
MPNST
Nephroblastoma
XPO1 Gene Mutation
Solid Tumor