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
4 other identifiers
interventional
97
1 country
36
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2023
Longer than P75 for phase_1
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 22, 2022
CompletedFirst Posted
Study publicly available on registry
June 27, 2022
CompletedStudy Start
First participant enrolled
March 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
May 5, 2026
May 1, 2026
4.3 years
June 22, 2022
May 2, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Recommended phase 2 dose (RP2D) (Phase I)
Any eligible patient who receives at least one dose of protocol-defined therapy will be considered evaluable for dose-limiting toxicity (DLT) if either of the following occurs: (1) the patient experiences a DLT during cycle 1 of therapy; or (2) the patient receives at least 4 doses of temozolomide and 1 dose of selinexor. All other patients enrolled during the phase 1 portion of the study will be considered inevaluable for DLT and may be replaced for the purposes of establishing the RP2D.
Up to 28 days
Progression-free survival (PFS) (Phase II)
Patients who experience disease progression or death will be considered to have experienced a PFS-event; otherwise the patient is considered censored at last contact.
From randomization to date of disease progression (either progression of existing lesions or appearance of new lesions), death, or date of last contact, whichever occurs first, assessed up to 3 years
Secondary Outcomes (4)
Response according to response assessment in neuro-oncology criteria (RANO) criteria
Up to 3 years
Six-month progression-free survival (PFS-6)
At 6 months
Median overall survival
Time between the date of randomization and the date of death or date of last contact, whichever occurs first, assessed up to 3 years
Molecular signatures of vulnerability
Up to 3 years
Study Arms (2)
Group I (temozolomide)
ACTIVE COMPARATORPatients receive temozolomide PO QD on days 1-5 of each cycle and placebo PO QD on days 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II (temozolomide, selinexor)
EXPERIMENTALPatients receive temozolomide PO QD on days 1-5 of each cycle and selinexor PO QD 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.
Interventions
Given PO
Given PO
Undergo MRI
Undergo blood sample collection
Eligibility Criteria
You may qualify if:
- 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
- +4 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07101, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Frances E Chow
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2022
First Posted
June 27, 2022
Study Start
March 20, 2023
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
May 5, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.