Selinexor in Patients With Advanced Thymic Epithelial Tumor Progressing After Primary Chemotherapy (SELECT)

A Phase 2, Open-label Study of Selinexor (KPT-330) in Patients With Advanced Thymic Epithelial Tumor (TET) Progressing After Primary Chemotherapy (SELECT)

The purpose of this study is to evaluate the safety, tolerability and effectiveness of selinexor in patients with advanced thymic epithelial tumor progressing after primary chemotherapy. This is a multicenter, open label phase II trial that uses a Simons two stage design. The study population is adults with histologically confirmed, advanced, inoperable TETs who are progressing after treatment with at least one platinum containing chemotherapy regimen.

This study is comprised of 2 similar phase II trials, one running in US (25 patients) and one running in EU (25 patients):

There are two study arms:

Arm A: Thymoma

• Stage 1: 15 patients
• Stage 2: 10 patients

Arm B: Thymic carcinoma

• Stage 1: 15 patients
• Stage 2: 10 patients

Study Overview

• Status: Terminated
• Conditions: Thymoma; Advanced Thymic Epithelial Tumor
• Intervention / Treatment: Drug: Open Label Selinexor

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Lombardi Comprehensive Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center - Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed advanced TET (thymoma)
• Progression after Primary Chemotherapy
• No more than two previous lines (Neoadjuvant or chemoradiotherapy will count as one line if disease progression has occurred within 6 months)
• Inoperable per local Investigator (Masaoka Stage III or IV)
• Progression after treatment with least one platinum containing chemotherapy regimen
• Measurable disease (RECIST 1.1)
• Age ≥18 years
• ECOG PS <2
• Patients must have recovered from the toxic effects of prior therapy at the time of initiation of the study drug unless toxicity is stable.
• A 4 weeks or five half lives interval from any investigational agents or cytotoxic chemotherapy to start of study is required
• Signed informed consent

• Adequate bone marrow function and organ function:

  • Hematopoietic function: total white blood cell count (WBC) ≥ 3000/mm³, absolute neutrophil count (ANC) ≥ 1500/mm³, platelet count ≥ 100,000/mm²; Hemoglobin > 9.0 gm/dL
  • Hepatic function: bilirubin < 1.5 times the upper limit of normal (ULN), ALT < 2.5 times ULN or ALT < 5.0 times ULN in the presence of liver metastases
  • Creatinine clearance > 30 ml/min according to Cockcroft-Gault
• Patients of childbearing potential must agree to use adequate birth control during and for 7 months after participation in this study

Exclusion Criteria:

• No significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy, including

  • Unstable cardiovascular function
  • Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
  • Markedly decreased visual acuity
  • Active infection requiring intravenous antibiotics
• Pregnancy or breast-feeding
• Symptomatic brain metastasis requiring corticosteroids
• Uncontrolled autoimmune disorders. Patients with autoimmune disorders under control on medication may be included. Patients with pure red cell aplasia may be included if haemoglobin levels are relatively stable on transfusions or medication
• Significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications
• No dehydration of NCI-CTCAE grade ≥ 1
• Serious psychiatric or medical conditions that could interfere with treatment.
• No history of organ allograft
• No concurrent therapy with approved or investigational anticancer therapeutics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selinexor; Open Label Selinexor 40 mg	Drug: Open Label Selinexor; Selinexor 40 mg oral tablets will be administered twice weekly, either on Monday/Wednesday, Tuesday/Thursday, Wednesday/Friday, Thursday/Saturday, or Friday/Sunday in a 3-weeks-on and 1-week-off schedule.; Other Names: KPT-330

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	To determine the overall response rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+ PR.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The number of adverse events as determined by Common Terminology Criteria for Adverse Events (CTCAEs) version 4.03	24 months
Overall Response Rate	To determine the overall response rate to according to modified ITMIG response criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT and MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	24 months
6 Month Progression Free Survival Rate	To determine six months progression free survival of patients with TET treated with selinexor	6 months
24 Month Overall Survival Rate	To determine overall survival of patients with TET treated with selinexor	24 months

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Hackensack Meridian Health; Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2018
• Primary Completion (Actual): July 27, 2020
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 10, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: KPT-330; Selinexor; Thymus
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Neoplasms by Site; Thoracic Neoplasms; Neoplasms, Complex and Mixed; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial
• Other Study ID Numbers: 2016-0622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No