Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Start Date
3/20/2023
Completion Date
6/30/2027
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.
Detailed Description
PRIMARY OBJECTIVES: 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 II) 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) 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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Magnetic Resonance Imaging
Placebo Administration
Selinexor
Temozolomide
Conditions
Locations
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