Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
NCT ID: NCT05432804
Last Updated: 2025-12-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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SUSPENDED
PHASE1/PHASE2
97 participants
INTERVENTIONAL
2023-03-20
2027-06-30
Brief Summary
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Detailed Description
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I. To determine the maximum tolerated dose of temozolomide followed by selinexor in recurrent glioblastoma patients as determined by dose-limiting toxicities (DLTs) and the total toxicity profile. (Phase I) II. To evaluate the efficacy of sequentially administering temozolomide and selinexor in recurrent glioblastoma as determined by progression-free survival (PFS). (Phase 2)
SECONDARY OBJECTIVES:
I. To evaluate overall response rate as determined by Response Assessment in Neuro-Oncology (RANO) response criteria.
II. To evaluate the efficacy of sequentially administering temozolomide and selinexor in recurrent glioblastoma as determined by 6-month PFS (6mPFS) and overall survival (OS).
III. To validate signatures of vulnerability to predict response to selinexor through ribonucleic acid (RNA) sequencing for 6 top-scoring gene pairs, whole exome sequencing, P53, EGFR, and Mcl-1.
OUTLINE: This is a phase I, dose-escalation study of selinexor in combination with fixed dose temozolomide followed by a phase II study that compares selinexor temozolomide combination therapy vs. temozolomide monotherapy. Patients are randomized to 1 of 2 groups for the phase II part of this trial.
GROUP I (Phase II): Patients receive temozolomide orally (PO) on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
GROUP II (Phase I and II): Patients receive temozolomide PO on days 1-5 of each cycle and selinexor PO on days 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Phase I completed as of April 2024)
Patients undergo magnetic resonance imaging (MRI) throughout the study and blood sample collection while on study.
After completion of study treatment, patients are followed up every 2 months up to 2 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group I (temozolomide)
Patients receive temozolomide PO on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study and blood sample collection while on study.
Biospecimen Collection
Undergo blood sample collection
Magnetic Resonance Imaging
Undergo MRI
Temozolomide
Given PO
Group II (temozolomide, selinexor)
Patients receive temozolomide PO on days 1-5 of each cycle and selinexor PO on days 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study and blood sample collection while on study.
Biospecimen Collection
Undergo blood sample collection
Magnetic Resonance Imaging
Undergo MRI
Selinexor
Given PO
Temozolomide
Given PO
Interventions
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Biospecimen Collection
Undergo blood sample collection
Magnetic Resonance Imaging
Undergo MRI
Selinexor
Given PO
Temozolomide
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Prior to resection or biopsy, patients must have measurable disease, defined as at least one bi-dimensional contrast-enhancing lesion with clearly defined margins, with 2 perpendicular diameters of at least 10 mm, visible on \>= 2 axial slices
* Patients must have received first-line treatment of temozolomide plus radiotherapy
* Patients must not have received any prior therapy aside from resection or biopsy for their recurrent disease
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of selinexor (KPT-330) in combination with temozolomide in patients \< 18 years of age, children are excluded from this study
* Karnofsky performance status \>= 60% (Eastern Cooperative Oncology Group \[ECOG\] =\< 2)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 10 g/dL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/ alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) =\< 3 x institutional ULN
* Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retro-viral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* The effects of selinexor (KPT-330) and temozolomide on the developing human fetus are unknown. For this reason and because selective nuclear export inhibitors as well as deoxyribonucleic acid (DNA) alkylating agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 180 days after the last dose of temozolomide. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of study treatment administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* Patients who have previously received bevacizumab
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor (KPT-330) or temozolomide
* History of hypersensitivity to dacarbazine (DTIC), since both dacarbazine and temozolomide are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC)
* Patients with uncontrolled intercurrent illness
* Pregnant women are excluded from this study because selinexor (KPT-330) is a selective inhibitor of nuclear export with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selinexor (KPT-330), breastfeeding is not allowed for mothers during treatment with selinexor (KPT-330) and for 7 days after the last dose. These potential risks may also apply to other agents used in this study
* Hospitalized patients with severe coronavirus disease of 2019 (COVID-19) who are \>= 75 years old, or with a high-risk COVID-GRAM score, or with lactate dehydrogenase (LDH) \> 370 (U/L) AND D-Dimer \> 600 mcg/L FEU should not receive low-dose selinexor (KPT-330) pending additional results
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Frances E Chow
Role: PRINCIPAL_INVESTIGATOR
City of Hope Comprehensive Cancer Center LAO
Locations
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Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Keck Medicine of USC Koreatown
Los Angeles, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Saint Barnabas Medical Center
Livingston, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Rutgers New Jersey Medical School
Newark, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
University of Virginia Cancer Center
Charlottesville, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Countries
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Other Identifiers
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NCI-2022-05066
Identifier Type: REGISTRY
Identifier Source: secondary_id
PHII-222
Identifier Type: -
Identifier Source: secondary_id
10505
Identifier Type: OTHER
Identifier Source: secondary_id
10505
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2022-05066
Identifier Type: -
Identifier Source: org_study_id