Selinexor in Patients With Advanced Thymoma and Thymic Carcinoma

Study Overview
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Brief Summary
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The aim of the study is to determine the efficacy of selinexor in adults with TETs determined by overall response rate (RECIST 1.1) in two parallel cohorts of patients with advanced thymomas or thymic carcinomas. The study is an international, multicenter, open label phase II trial using Simons two stage design. The study population is adults with histologically confirmed, advanced, inoperable TETs who are progressing after treatment with least one platinum containing chemotherapy regimen. This study is comprised of 2 similar phase II tirals, one running in EU (25 patients) and one running in US (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

Detailed Description
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Not provided

Official Title
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A Phase II Study of Selinexor (KPT-330) in Patients With Advanced Thymic Epithelial Tumour (TET) Progressing After Primary Chemotherapy.

Conditions
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Thymoma, Advanced Thymic Epithelial Tumour

Intervention / Treatment
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* Drug: Selinexor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced TET (thymoma or thymic carcinoma) Inoperable per local Investigator (Masaoka Stage III or IV) Progression after treatment with least one platinum containing chemotherapyregimen 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 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 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 3 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 Any other cancer (excluding radically operated localised squamous skin cancer) with clinical activity within the last 2 years 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

| Intervention/Treatment |
| --- |
|Drug: Selinexor|Selinexor 60 mg oral tablets will be administered twice weekly, either Monday/Wednesday or on Tuesday/Thursday or on Wednesday/Friday in a 3-weeks-on and 1-week-off Schedule.|

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 according to RECIST 1.1 | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | To determine six months progression free survival of patients with TET treated with selinexor | 6 months | 
| Adverse Events | The number of adverse events as determined by Common Terminology Criteria for Adverse Events (CTCAEs) version 4.03 | 24 months |