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

NCT ID: NCT01986348

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-03
• Study Completion Date: 2020-01-23

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.

Conditions

Glioblastoma; Glioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Selinexor 60 mg and Surgery

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

One cycle is 28 days (4 weeks).

Arm B: Selinexor 50 mg/m^2

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

One cycle is 28 days (4 weeks).

Arm C: Selinexor 60 mg

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

One cycle is 28 days (4 weeks).

Arm D: Selinexor 80 mg

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

One cycle is 28 days (4 weeks).

Interventions

Selinexor

One cycle is 28 days (4 weeks).

Intervention Type: DRUG

Other Intervention Names

KPT-330

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

University of Groningen Faculty of Medical Sciences, Medical Oncology

Groningen, , Netherlands

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

Rotterdam, , Netherlands

Countries

United States; Denmark; Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KCP-330-004

Identifier Type: -

Identifier Source: org_study_id