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

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ClinicalTrials.gov Identifier: NCT01986348
Recruitment Status : Active, not recruiting
First Posted : November 18, 2013
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

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. Patients have been enrolled in Arms A, B and C, but Arm D is the only arm currently open to recruiting patients.

Condition or disease Intervention/treatment Phase
Glioblastoma Glioma Drug: Selinexor Phase 2

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 or above 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 : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas
Study Start Date : March 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
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.
Drug: Selinexor
One cycle is 28 days (4 weeks).
Other Name: KPT-330

Experimental: Arm C: Selinexor only
Patients who were not eligible for surgery may be randomized to take selinexor twice weekly.
Drug: Selinexor
One cycle is 28 days (4 weeks).
Other Name: KPT-330

Experimental: Arm D: Selinexor only
Patients who were not eligible for surgery may be randomized to take selinexor once weekly.
Drug: Selinexor
One cycle is 28 days (4 weeks).
Other Name: KPT-330




Primary Outcome Measures :
  1. 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 Response Assessment in Neuro-Oncology (RANO) criteria



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01986348


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute, Center for Neuro-Oncology
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University, Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
Denmark
The Phase I Unit, Dept. of Oncology, Rigshospitalet
Copenhagen, Denmark, DK-2100
Netherlands
University of Groningen Faculty of Medical Sciences, Medical Oncology
Groningen, Netherlands, 9713 GZ
Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit
Rotterdam, Netherlands, 3008AE
Sponsors and Collaborators
Karyopharm Therapeutics Inc
Investigators
Principal Investigator: Morten Mau-Sørensen, MD, Ph.D The Phase I Unit, Dept. of Oncology, Rigshospitalet
Principal Investigator: Andrew B Lassman, MD Columbia University

Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT01986348     History of Changes
Other Study ID Numbers: KCP-330-004
First Posted: November 18, 2013    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Karyopharm Therapeutics Inc:
GBM
Glioblastoma
selinexor
KPT-330
Karyopharm
brain tumor
brain cancer
Glioma
Astrocytoma
Oligodendrogliomas
Oligo-astrocytomas

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue