Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
A Phase 1 and Randomized Phase 2 Trial of Selinexor and Temozolomide in Recurrent Glioblastoma
- Recurrent Glioblastoma, IDH-Wildtype
- Recurrent MGMT-Methylated Glioblastoma
At a glance
- Phase
- Phase 1
- Study type
- Interventional
- Sponsor
- National Cancer Institute (NCI)
- Enrolment target
- 97
- Started
- 20 March 2023
- Main results due
- 30 June 2027
- Study sites
- 36
- Registry updated
- 28 September 2026
Can you take part?
- Aged 18 years and over.
- Open to any sex.
- You need the condition being studied — healthy volunteers are not accepted.
These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.
Read the full eligibility criteria
Inclusion Criteria: * Patients must have histologically confirmed glioblastoma (IDH wild-type, MGMT promoter methylated) that has undergone resection or biopsy upon first recurrence. Recurrence at site of prior involvement is defined by histopathological evidence of viable neoplastic cells associated with any of the following: mitotic activity, increased proliferation rate, micro-endothelial proliferation, or pseudo-palisading necrosis * 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-retroviral 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 had chemotherapy must have full recovery of organ and marrow function following the nadir of the last chemotherapy cycle * 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
What this study is about
In the sponsor’s own words, from the registry.
This phase I/II trial tests the safety, side effects and best dose of selinexor given in combination with the usual chemotherapy (temozolomide) and compares the effect of this combination therapy versus the usual chemotherapy alone (temozolomide) in treating patients with glioblastoma that has come back (recurrent). Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may keep cancer cells from growing and may kill them. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Giving selinexor in combination with usual chemotherapy (temozolomide) may shrink or stabilize the tumor better than the usual chemotherapy with temozolomide alone in patients with recurrent glioblastoma.
Study sites(36)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, United States
Recruiting
Keck Medicine of USC Koreatown
Los Angeles, California, United States
Suspended
Los Angeles General Medical Center
Los Angeles, California, United States
Suspended
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Suspended
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Recruiting
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
Recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, United States
Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Recruiting
Moffitt Cancer Center
Tampa, Florida, United States
Recruiting
Emory University Hospital Midtown
Atlanta, Georgia, United States
Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Recruiting
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Recruiting
Cooperman Barnabas Medical Center
Livingston, New Jersey, United States
Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Recruiting
Rutgers New Jersey Medical School
Newark, New Jersey, United States
Suspended
Roswell Park Cancer Institute
Buffalo, New York, United States
Active, not recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States
Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, United States
Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Recruiting
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
Suspended
University of Virginia Cancer Center
Charlottesville, Virginia, United States
Active, not recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Active, not recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, United States
Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Recruiting
Showing 36 of 36 sites. 28 of the 36 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.
Source: ClinicalTrials.gov record NCT05432804. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.
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