Clinical trial NCT01986348: Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Participants With Recurrent Gliomas
Official title: A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioblastoma
Glioma
Keywords: GBM
Glioblastoma
selinexor
KPT-330
Karyopharm
brain tumor
brain cancer
Glioma
Astrocytoma
Oligodendrogliomas
Oligo-astrocytomas
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2013-11-18
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 6-Month Progression-Free Survival (PFS) Rate
timeFrame: From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 71 months
measure: Overall Survival (OS)
timeFrame: From date of study treatment up to date of death (assessed up to 71 months)
measure: Progression-free Survival (PFS)
timeFrame: From start of study treatment up to disease progression (assessed up to 71 months)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study treatment administration up to 71 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute, Center for Neuro-Oncology
state: Massachusetts
city: New York
country: United States
facility: Columbia University, Herbert Irving Comprehensive Cancer Center
state: New York
city: Copenhagen
country: Denmark
facility: The Phase I Unit, Dept. of Oncology, Rigshospitalet
city: Groningen
country: Netherlands
facility: University of Groningen Faculty of Medical Sciences, Medical Oncology
city: Rotterdam
country: Netherlands
facility: Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit
Study officials:
References: