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

Study Overview
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Brief Summary
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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

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

Conditions
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Thymoma, Advanced Thymic Epithelial Tumor

Intervention / Treatment
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* Drug: Open Label Selinexor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selinexor<br>Open Label Selinexor 40 mg | Drug: Open Label Selinexor<br>* 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.<br>* Other names: KPT-330;|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Adverse Events | The number of adverse events as determined by Common Terminology Criteria for Adverse Events (CTCAEs) version 4.03 | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thymus, Selinexor, KPT-330