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Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Participants With Recurrent Gliomas (KING)

Primary Purpose

Glioblastoma, Glioma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Selinexor
Sponsored by
Karyopharm Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring GBM, Glioblastoma, selinexor, KPT-330, Karyopharm, brain tumor, brain cancer, Glioma, Astrocytoma, Oligodendrogliomas, Oligo-astrocytomas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathologically confirmed GBM (including all histologic variants) at first diagnosis with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide;
  • 18 years of age or older
  • Participants enrolling in the medical arm (Arms B, C and D) must be on a stable or decreasing dose of corticosteroids (or none) for at least 5 days prior to the baseline MRI;
  • Measurable disease (according to RANO guidelines)
  • Surgical arm (Arm A) must be predicted pre-operatively to have sufficiently sized tumor to be resected and provide tissue samples for exploratory assessments.

Exclusion Criteria:

  • Markedly decreased visual acuity if attributed to other causes than GBM.
  • Known active hepatitis A, B, or C
  • Participants with coagulation problems and medically significant bleeding in the month prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding). Prior history of DVT or PE is not exclusionary.
  • Participants must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medications.
  • Prior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any question of the definition of a direct VEGF/VEGFR inhibitor, consult Sponsor.
  • Arms C and D only: body surface area < 1.2 m².
  • < 24 days from prior temozolomide, < 6 weeks from nitrosourea, < 4 weeks from other chemotherapy or investigational agents prior to start of treatment within study.

Sites / Locations

  • Massachusetts General Hospital
  • Dana Farber Cancer Institute, Center for Neuro-Oncology
  • Columbia University, Herbert Irving Comprehensive Cancer Center
  • The Phase I Unit, Dept. of Oncology, Rigshospitalet
  • University of Groningen Faculty of Medical Sciences, Medical Oncology
  • Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm A: Selinexor 60 mg and Surgery

Arm B: Selinexor 50 mg/m^2

Arm C: Selinexor 60 mg

Arm D: Selinexor 80 mg

Arm Description

Participants who required surgery received up to 3 doses of oral selinexor tablets 60 milligrams (mg) twice weekly (BIW) on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until progression of disease (PD) or development of unacceptable toxicities.

Participants who were not eligible for surgery received selinexor tablets 50 mg per square meter (mg/m^2) BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.

Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.

Participants who were not eligible for surgery received selinexor tablets 80 mg once weekly (QW) during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
October 17, 2013
Last Updated
January 24, 2023
Sponsor
Karyopharm Therapeutics Inc
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1. Study Identification

Unique Protocol Identification Number
NCT01986348
Brief Title
Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Participants With Recurrent Gliomas
Acronym
KING
Official Title
A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated due to Sponsor decision (all except 1 patient were off-treatment and 2 patients were in survival follow-up)
Study Start Date
March 3, 2014 (Actual)
Primary Completion Date
January 23, 2020 (Actual)
Study Completion Date
January 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Karyopharm Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Glioma
Keywords
GBM, Glioblastoma, selinexor, KPT-330, Karyopharm, brain tumor, brain cancer, Glioma, Astrocytoma, Oligodendrogliomas, Oligo-astrocytomas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Selinexor 60 mg and Surgery
Arm Type
Experimental
Arm Description
Participants who required surgery received up to 3 doses of oral selinexor tablets 60 milligrams (mg) twice weekly (BIW) on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until progression of disease (PD) or development of unacceptable toxicities.
Arm Title
Arm B: Selinexor 50 mg/m^2
Arm Type
Experimental
Arm Description
Participants who were not eligible for surgery received selinexor tablets 50 mg per square meter (mg/m^2) BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Arm Title
Arm C: Selinexor 60 mg
Arm Type
Experimental
Arm Description
Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Arm Title
Arm D: Selinexor 80 mg
Arm Type
Experimental
Arm Description
Participants who were not eligible for surgery received selinexor tablets 80 mg once weekly (QW) during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
KPT-330
Intervention Description
One cycle is 28 days (4 weeks).
Primary Outcome Measure Information:
Title
6-Month Progression-Free Survival (PFS) Rate
Description
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)
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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
Title
Overall Survival (OS)
Description
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)
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
From start of study treatment up to disease progression (assessed up to 71 months)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically confirmed GBM (including all histologic variants) at first diagnosis with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide; 18 years of age or older Participants enrolling in the medical arm (Arms B, C and D) must be on a stable or decreasing dose of corticosteroids (or none) for at least 5 days prior to the baseline MRI; Measurable disease (according to RANO guidelines) Surgical arm (Arm A) must be predicted pre-operatively to have sufficiently sized tumor to be resected and provide tissue samples for exploratory assessments. Exclusion Criteria: Markedly decreased visual acuity if attributed to other causes than GBM. Known active hepatitis A, B, or C Participants with coagulation problems and medically significant bleeding in the month prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding). Prior history of DVT or PE is not exclusionary. Participants must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medications. Prior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any question of the definition of a direct VEGF/VEGFR inhibitor, consult Sponsor. Arms C and D only: body surface area < 1.2 m². < 24 days from prior temozolomide, < 6 weeks from nitrosourea, < 4 weeks from other chemotherapy or investigational agents prior to start of treatment within study.
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute, Center for Neuro-Oncology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Columbia University, Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
The Phase I Unit, Dept. of Oncology, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
Facility Name
University of Groningen Faculty of Medical Sciences, Medical Oncology
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit
City
Rotterdam
ZIP/Postal Code
3008AE
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Participants With Recurrent Gliomas

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