A Study of Different Dosing Schedules of Selinexor in Sarcoma Patients

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional guidelines
2. Age \> 18 years.
3. Patients must have histologically confirmed locally advanced/unresectable or metastatic STS

   1. For Arm A the acceptable histologies are MPNST, ESS and LMS
   2. For Arm B arm all STS histologies are eligible
4. Patients must fall into one of the three following categories:

   1. Show evidence of progressive disease on study entry; or
   2. Be treatment naïve, but have progressed since diagnosis; or
   3. Newly diagnosed patients with de novo metastatic measurable disease.
5. Patient must have measureable disease as defined by RECIST 1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
7. Adequate hematopoietic function within 7 days prior to C1D1:

   1. absolute neutrophil count (ANC) ≥1.0x109/L
   2. hemoglobin ≥ 90 g/L
   3. platelet count ≥100 x 109/L
   4. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.
   5. Patients must have:

   i. At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and

   ii. At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.

   iii. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
8. Adequate hepatic function within 28 days prior to C1D1:

   1. Bilirubin \<1.5 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 times ULN)
   2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2 X ULN. In the case of known (radiological and/or biopsy documented) liver metastasis, ALT/AST \<5.0 X ULN is acceptable;
9. Adequate renal function within 28 days prior to C1D1: estimated creatinine clearance of ≥20 mL/min calculated using the formula of Cockcroft and Gault: (140-Age)(Weight in kg)(Constant)/(serum creatinine µmol/L); where constant is 1.23 for men and by 1.04 for women.
10. Female patients of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at Screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
11. Ability to swallow pills

Exclusion Criteria:

1. Has received selinexor or another XPO1 inhibitor previously
2. Patients who are pregnant or lactating
3. Radiation (except planned or on-going palliative radiation outside of the region of measurable disease), chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy. Mitomycin C and radio-immunotherapy within 6 weeks prior to cycle 1 day 1.
4. Major surgery within 4 weeks before initiation of therapy
5. Active, ongoing or uncontrolled active infection within one week prior to first dose
6. Patients with any gastrointestinal dysfunctions that could interfere with the absorption of Selinexor or patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea;
7. Inability or unwillingness to take supportive medications such as anti-nausea and anti anorexia agents as recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Antiemesis and Palliative Care.
8. In the opinion of the Investigator, patients who are significantly below their ideal body weight (Body Surface Area ≤ 1.2m2)
9. Concurrent therapy with approved or investigational anticancer therapeutic agents
10. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results