Selinexor in Patients With Advanced Thymic Epithelial Tumor Progressing After Primary Chemotherapy
Condition: Thymoma; Advanced Thymic Epithelial Tumor
MeSH terms: Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial
Intervention: Open Label Selinexor
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Thymus; Selinexor; KPT-330

Summary:

      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
    

Eligibility criteria:

        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