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A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas (KING)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01986348
Recruitment Status : Completed
First Posted : November 18, 2013
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE October 17, 2013
First Posted Date  ICMJE November 18, 2013
Last Update Posted Date May 20, 2020
Study Start Date  ICMJE March 2014
Actual Primary Completion Date January 23, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2020)
Number of patients with 6 months of progression-free survival (6mPFS) in Arms B, C, and D [ Time Frame: 6 months ]
Progression will be determined by the Response Assessment in Neuro-Oncology (RANO) criteria
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2013)
Determine the efficacy of selinexor in adults with recurrent GBM [ Time Frame: The analysis of 6-month PFS will be performed on patients that have not progressed or died at 6 months following the start of therapy ]
Progression will be determined by the RANO criteria
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2013)
Response to therapy [ Time Frame: 6 months following the start of therapy ]
Determined by median overall survival (OS) and median progression-free survival (PFS).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 11, 2013)
Pharmacokinetics [ Time Frame: Surgical Arm- blood drawn on day of surgery: pre-dose, 1 hr and 2 hrs post dose and approximately the same time as resection of the tumor. Nonsurgical arm- Cycle 2 Day 1 only at pre-dose, 2 hr and 4 hrs post dose. ]
Blood samples pre- and post-dosing will be analyzed for cytokine concentrations and XPO1 inhibition in leukocytes.
 
Descriptive Information
Brief Title  ICMJE A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas
Official Title  ICMJE A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas
Brief Summary This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in patients with recurrent gliomas.
Detailed Description

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

Initially, the study included 2 arms: an exploratory Surgical Arm (Arm A) with sequential enrollment for patients who require surgery and a medical arm (Arm B) for patients 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 patients were ever enrolled in these arms.

Patients in the primary population enrolled under Protocol Version ≥ 4.0 will be randomized to Arm C and Arm D (approximately 30 patients per arm) to explore alternative dosing to potentially improve tolerability.

After screening and registration/randomization in the study, patients enrolling in Arm A or randomized to Arm C will receive 60 mg selinexor orally twice weekly. Patients randomized to Arm D will receive 80 mg selinexor orally weekly.

Patients will be treated until progression of disease or the development of unacceptable toxicities. All patients will then undergo the End of Treatment (EOT) visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Glioma
Intervention  ICMJE Drug: Selinexor
One cycle is 28 days (4 weeks).
Other Name: KPT-330
Study Arms  ICMJE
  • Experimental: Arm A: Selinexor and surgery
    Patients who require surgery will receive up to 3 doses of selinexor, undergo surgery, and resume selinexor after recovery. Selinexor will be given twice weekly.
    Intervention: Drug: Selinexor
  • Experimental: Arm C: Selinexor only
    Patients who were not eligible for surgery may be randomized to take selinexor twice weekly.
    Intervention: Drug: Selinexor
  • Experimental: Arm D: Selinexor only
    Patients who were not eligible for surgery may be randomized to take selinexor once weekly.
    Intervention: Drug: Selinexor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 31, 2018)
76
Original Estimated Enrollment  ICMJE
 (submitted: November 11, 2013)
30
Actual Study Completion Date  ICMJE January 23, 2020
Actual Primary Completion Date January 23, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Patients enrolling in the medical arm (Arms 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
  • Patients 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.
  • Patients 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01986348
Other Study ID Numbers  ICMJE KCP-330-004
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Karyopharm Therapeutics Inc
Study Sponsor  ICMJE Karyopharm Therapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Morten Mau-Sørensen, MD, Ph.D The Phase I Unit, Dept. of Oncology, Rigshospitalet
Principal Investigator: Andrew B Lassman, MD Columbia University
PRS Account Karyopharm Therapeutics Inc
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP