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

NCT01986348 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: KCP-330-004
• Study Type: interventional
• Target: 76
• Locations: 3 countries
• Sites: 6

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.

Conditions

Glioblastoma; Glioma

Keywords

GBM; Glioblastoma; selinexor; KPT-330; Karyopharm; brain tumor; brain cancer; Glioma; Astrocytoma; Oligodendrogliomas; Oligo-astrocytomas

Outcome Measures

Primary Outcomes (1)

• 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.

  From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6)

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to 71 months

• Overall Survival (OS)

  From date of study treatment up to date of death (assessed up to 71 months)

• Progression-free Survival (PFS)

  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)

  From start of study treatment administration up to 71 months

Study Arms (4)

Arm A: Selinexor 60 mg and Surgery

EXPERIMENTAL

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.

Drug: Selinexor

Arm B: Selinexor 50 mg/m^2

EXPERIMENTAL

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.

Drug: Selinexor

Arm C: Selinexor 60 mg

EXPERIMENTAL

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.

Drug: Selinexor

Arm D: Selinexor 80 mg

EXPERIMENTAL

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.

Drug: Selinexor

Interventions

Selinexor DRUG

One cycle is 28 days (4 weeks).

Also known as: KPT-330

Arm A: Selinexor 60 mg and Surgery; Arm B: Selinexor 50 mg/m^2; Arm C: Selinexor 60 mg; Arm D: Selinexor 80 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed GBM (including all histologic variants) at first diagnosis with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide;
• 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.

You may not qualify if:

• Markedly decreased visual acuity if attributed to other causes than GBM.
• Known active hepatitis A, B, or C
• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (6)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute, Center for Neuro-Oncology

Boston, Massachusetts, 02215, United States

Location

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

The Phase I Unit, Dept. of Oncology, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

University of Groningen Faculty of Medical Sciences, Medical Oncology

Groningen, 9713 GZ, Netherlands

Location

Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit

Rotterdam, 3008AE, Netherlands

Location

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma; Oligodendroglioma

Interventions

selinexor

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Study was terminated due to Sponsor decision (all except 1 patient were off-treatment and 2 patients were in survival follow-up).

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc.

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: November 18, 2013
• Study Start: March 3, 2014
• Primary Completion: January 23, 2020
• Study Completion: January 23, 2020
• Last Updated: January 26, 2023
• Results First Posted: August 2, 2021

Record last verified: 2023-01

Locations

DK (1); NL (2); US (3)