Recurrent Glioblastoma, IDH-WildtypePhase 1/2NCT05432804
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 1/2 study testing Biospecimen Collection, Magnetic Resonance Imaging and Selinexor in people with Recurrent Glioblastoma, IDH-Wildtype and Recurrent MGMT-Methylated Glioblastoma, run by National Cancer Institute (NCI) at 39 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
- What is being tested?
- Biospecimen Collection, Magnetic Resonance Imaging and Selinexor
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 97 participants
- Where
- 39 sitesUnited States
- Study dates
- 20 Mar 2023to 30 Jun 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
39 sites in 1 country. Contact the study team or a site near you to ask about taking part.
39 sites in 1 country
United States39 sites, 35 recruiting
- Recruiting
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Site Public Contact, 888-946-7447
Kimberly Hoang
- Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Site Public Contact, 404-778-1868
Kimberly Hoang
- Recruiting
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Site Public Contact, 720-848-0650
Denise M. Damek
- Active, not recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
- Active, not recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Lauren Singer
- Recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Site Public Contact, 513-584-7698, cancer@uchealth.com
Lalanthica V. Yogendran
- Recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Site Public Contact, 866-223-8100, TaussigResearch@ccf.org
David M. Peereboom
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Pierre Giglio
- Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Site Public Contact, 800-826-4673, becomingapatient@coh.org
Jana L. Portnow
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Frances E. Chow
- Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Site Public Contact, 855-776-0015
Sani H. Kizilbash
- Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Site Public Contact, 858-822-5354, cancercto@ucsd.edu
David E. Piccioni
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
John L. Villano
- Recruiting
Cooperman Barnabas Medical Center
Livingston, New Jersey, 07039
Site Public Contact, 973-322-5200
Andrew B. Brown
- Recruiting
Keck Medicine of USC Koreatown
Los Angeles, California, 90020
Site Public Contact, 213-388-0908
Jacob S. Thomas
- Recruiting
Los Angeles General Medical Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451, uscnorrisinfo@med.usc.edu
Jacob S. Thomas
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Jacob S. Thomas
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Ankush Bhatia
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Ankush Bhatia
- Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Site Public Contact, 732-235-7356
Andrew B. Brown
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Site Public Contact, CancerTrials@nyulangone.org
Jose R. McFaline Figueroa
- Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Peter C. Pan
- Recruiting
Rutgers New Jersey Medical School
Newark, New Jersey, 07101
Site Public Contact, 732-235-7356
Andrew B. Brown
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
James D. Battiste
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Frances E. Chow
- Recruiting
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Lauren Singer
- Recruiting
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Alyx B. Porter Umphrey, 507-538-7623, porter.alyx@mayo.edu
Alyx B. Porter Umphrey
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Megan Mantica
- Active, not recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Sani H. Kizilbash
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Orwa Aboud
- Suspended
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Patrick T. Grogan
- Recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Site Public Contact, 513-584-7698, cancer@uchealth.com
Lalanthica V. Yogendran
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Roy E. Strowd
About this study
Official title: A Phase 1 and Randomized Phase 2 Trial of Selinexor and Temozolomide in Recurrent Glioblastoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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 II)
SECONDARY OBJECTIVES:
- 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) once daily (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 (Phase I and II): Patients 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. (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.
- Being tested
- Biospecimen Collection, Magnetic Resonance Imaging, Placebo Administration, Selinexor, Temozolomide
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Placebo AdministrationDrug
Given PO
SelinexorDrug
Also called ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT 330, KPT-330
Given PO
TemozolomideDrug
Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Group I (temozolomide) | Active comparator | Patients 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. Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Drug: Placebo Administration; Drug: Temozolomide |
| Group II (temozolomide, selinexor) | Experimental | Patients 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. Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Drug: Selinexor; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
A patient who is evaluated as complete response, partial response, or stable disease will be considered a RANO-responder. All other patients will be considered RANO-non-responders. Response rate will be calculated and comparisons made using categorical data methods.
Measured: Up to 3 years
Six-month progression-free survival (PFS-6)
Any patient considered evaluable for RANO response will be considered evaluable for PFS-6. Any evaluable patient who is considered progression free for the primary analysis will be considered a PFS-6 responder. All other evaluable patients will be considered PFS-6 non-responders.
Measured: At 6 months
Median overall survival
Will be calculated from the Kaplan-Meier estimate of the probability of death as a function of time since enrollment. Ninety-five percent (95%) confidence intervals will be calculated as well.
Measured: 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
Will be assessed using logistic regression for the outcome measure (RANO response) and using proportional hazard regression with the biological characteristic of interest as the predictor variable for risk for PFS event. Patients considered evaluable for RANO response and PFS, respectively, will contribute to the analyses for these exploratory outcomes. Two-sided statistical testing will be employed, and a p-value of 0.05 or less will be considered as indicating significant evidence of association between the particular signature and the outcome of interest.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2022
- Study start20 Mar 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Glioblastoma, IDH-WildtypeStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 97 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jana L Portnow, Principal investigator, City of Hope Comprehensive Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05432804
- Sponsor's protocol ID
- NCI-2022-05066
- Other IDs
- NCI-2022-05066, PHII-222, 10505, 10505, UM1CA186717
- Status last verified
- Aug 2026
- First submitted
- 22 Jun 2022
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.