Selinexor in Combination With Ixazomib for the Treatment of Advanced Sarcoma

Inclusion Criteria

• •1. Signed written informed consent.
• •2. Age ≥ 14 years
• •3. Body surface area ≥ 1.2 m2
• •4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• •6. Disease which is locally advanced and unresectable or metastatic. Disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligible.
• •7. Measurable disease as assessed by RECIST criteria version 1.1.
• •8. Progression on, or intolerance to, at least one prior systemic regimen for sarcoma (including systemic treatment used in the adjuvant or neoadjuvant settings). For alveolar soft part sarcoma and dedifferentiated liposarcoma, there is no upper limit on the number of prior therapies that may have been received. For Ewing sarcoma and malignant peripheral nerve sheath tumor, patients may have received no more than 3 prior lines of therapy (excluding systemic treatment used in the adjuvant or neoadjuvant settings).
• •9. Acceptable organ and marrow function as defined below:
• •Absolute neutrophil count (ANC) ≥ 1,500/mm3 Hemoglobin ≥ 8.5 g/dL Platelet count ≥ 100,000/mm3 Calculated creatinine clearance \> 30 mL/min Total bilirubin ≤ 1.5 times upper limit of normal Aspartate Transaminase (AST) /Alanine Transaminase (ALT) ≤ 3.0 times upper limit of normal
• •* Upper limit of normal is defined by the clinical laboratory performing the test.
• •* Creatinine clearance is obtained using the lean body mass formula (Modified Cockcroft Gault)
• •* If transaminase elevation and/or bilirubin elevation is attributed to the presence of liver metastases, a total bilirubin ≤ 2.5 times the upper limit of normal and an Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 times the upper limit of normal are permissible. Patients with an elevated bilirubin level that is attributed to an inherited disorder, such as Gilbert's disease, may be enrolled at the discretion of the principal investigator.
• •* Patients may not receive platelet transfusions within 3 weeks of initiating protocol therapy.
• •10. Meet the following criteria regarding contraception:
• •Female patients who:
• •1. Are postmenopausal for at least 1 year before the screening visit, OR
• •2. Are surgically sterile, OR
• •3. If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
• •4. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• •Male patients who: (must meet criteria even if surgically sterilized, i.e. after vasectomy):
• •1. Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
• •2. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)