This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas.
This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas. Initially, the study included 2 arms: an exploratory Surgical Arm (Arm A) with sequential enrollment for participants who require surgery and a medical arm (Arm B) for participants who are not eligible for surgery. Enrollment in Arm B was stopped to explore alternative dosing in Protocol Versions ≥ 4.0 to potentially improve tolerability. Four arms (Arms C, D, E, and F) were added to the Medical Arm in Protocol Version 4.0. Arms E and F were eliminated in protocol version 6.0 and no participants were ever enrolled in these arms. Participants in the primary population enrolled under Protocol Version ≥ 4.0 will be randomized to Arm C and Arm D (approximately 30 participants per arm) to explore alternative dosing to potentially improve tolerability. After screening and registration/randomization in the study, participants enrolling in Arm A or randomized to Arm C will receive 60 mg selinexor orally twice weekly. Participants randomized to Arm D will receive 80 mg selinexor orally weekly. Participants will be treated until progression of disease or the development of unacceptable toxicities. All participants will then undergo the End of Treatment (EOT) visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
76
One cycle is 28 days (4 weeks).
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute, Center for Neuro-Oncology
Boston, Massachusetts, United States
Columbia University, Herbert Irving Comprehensive Cancer Center
New York, New York, United States
The Phase I Unit, Dept. of Oncology, Rigshospitalet
Copenhagen, Denmark
6-Month Progression-Free Survival (PFS) Rate
The analysis of 6mPFS was performed by calculating the estimated survival probability of having PFS ≥ 6 months based on Kaplan-Meier method, where PFS was defined as the time from the start of study treatment until first documented progression based on Response Assessment in Neuro-Oncology (RANO) criteria, or death from any cause. Progressive disease occurs when either of the criteria was present: greater than or equal to (≥) 25 percentage (%) increase in T1 gadolinium enhancing disease, increase in T2/ Fluid-attenuated inversion recovery (FLAIR), detection of new lesions, or decreased clinical status.
Time frame: From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6)
Overall Response Rate (ORR)
The ORR was determined as percentage of participants who had either complete response (CR) or partial response (PR) using the RANO criteria. CR: No T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, no corticosteroid use and stable, or increasing clinical status. PR: ≥50% decrease in T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, stable or decreased use of corticosteroids, and stable or increased clinical status.
Time frame: Up to 71 months
Overall Survival (OS)
The OS was calculated from the date of start of study treatment to the date of death. Participants who were still alive prior to the data cut-off for final efficacy analysis, or who dropout prior to study end, were censored on the day they were last known to be alive. The OS was estimated using Kaplan-Meier method.
Time frame: From date of study treatment up to date of death (assessed up to 71 months)
Progression-free Survival (PFS)
The PFS was calculated from the date of start of study treatment to the date of disease progression based on RANO criteria, or date of death should progression not have occurred. Progressive disease occurs when either of the criteria was present: ≥25% increase in T1 gadolinium enhancing disease, increased T2/FLAIR, detection of new lesions, or decreased clinical status.
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University of Groningen Faculty of Medical Sciences, Medical Oncology
Groningen, Netherlands
Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit
Rotterdam, Netherlands
Time frame: From start of study treatment up to disease progression (assessed up to 71 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as an AE that was fatal; life threatening (places the participant at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; and other important medical events. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study medication through 30 days following last dose or any event considered drug-related by the Investigator through the end of the study. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study treatment administration up to 71 months