Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment

Inclusion Criteria:

• Patients must have histologically confirmed glioblastoma (IDH wild-type, MGMTpromoter methylated) that has undergone resection or biopsy upon first recurrence.Recurrence at site of prior involvement is defined by histopathological evidence ofviable neoplastic cells associated with any of the following: mitotic activity,increased proliferation rate, micro-endothelial proliferation, or pseudo-palisadingnecrosis

• Prior to resection or biopsy, patients must have measurable disease, defined as atleast 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 fortheir recurrent disease

• Age >= 18 years. Because no dosing or adverse event data are currently available onthe use of selinexor (KPT-330) in combination with temozolomide in patients < 18years 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 xinstitutional ULN

• Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retro-viraltherapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification. To beeligible for this trial, patients should be class 2B or better

• The effects of selinexor (KPT-330) and temozolomide on the developing human fetusare unknown. For this reason and because selective nuclear export inhibitors as wellas deoxyribonucleic acid (DNA) alkylating agents are known to be teratogenic, womenof child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry andfor the duration of study participation, and for 180 days after the last dose oftemozolomide. Should a woman become pregnant or suspect she is pregnant while she orher partner is participating in this study, she should inform her treating physicianimmediately. Men treated or enrolled on this protocol must also agree to useadequate 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 consentdocument. Participants with impaired decision-making capacity who have alegally-authorized representative (LAR) and/or family member available will also beeligible

Exclusion Criteria:

• Patients who have had chemotherapy must have full recovery of organ and marrowfunction 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 orbiologic composition to selinexor (KPT-330) or temozolomide

• History of hypersensitivity to dacarbazine (DTIC), since both dacarbazine andtemozolomide 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 aselective inhibitor of nuclear export with the potential for teratogenic orabortifacient effects. Because there is an unknown but potential risk for adverseevents 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 applyto 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