Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma (SeliSarc)

Inclusion Criteria:

1. Patients must provide written informed consent prior to performance of anystudy-specific procedures and must be willing to comply with treatment and follow-up.Informed consent must be obtained prior to start of the screening process. Proceduresconducted as part of the patient's routine clinical management (e.g. imaging tests),obtained prior to signature of informed consent may be used for screening or baselinepurposes as long as these procedures are conducted as specified in the protocol.
2. Age: 18-80 years.
3. Histologic diagnosis of soft tissue sarcoma (leiomyosarcoma or malignant peripheralnerve sheath tumor) confirmed by central pathology review prior to enrolment with anarchive tumor sample. A fresh paraffin embedded tumor tissue block must be providedfor all subjects for biomarker analysis before and (when feasible) after treatmentwith investigational products.
4. Metastatic/advanced disease in progression in the last 6 months.
5. Patients have previously received at least one previous line of systemic therapy.
6. Measurable disease according to RECIST 1.1 criteria.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
8. Adequate hepatic, renal, cardiac, and hematologic function.
9. Laboratory tests as follows:

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 1.5 mg/dL 10. Left ventricular ejection fraction ≥ 50% byechocardiogram or MUGA scan.

11. Females of childbearing potential must have a negative serum or urine pregnancy testwithin 72 hours prior to enrollment and agree to use birth control measures during studytreatment and for 3 months after its completion. Patients must not be pregnant or nursingat study entry. Women/men of reproductive potential must have agreed to use an effectivecontraceptive method.

Exclusion Criteria:

1. Three or more systemic treatment lines (including both chemotherapy and targetedtherapy) for advanced disease (localized unresectable or metastatic).
2. Patients who have received any other anti-cancer therapy or investigational product inthe last 21 days prior to enrollment.
3. Prior malignancy that required treatment or has shown evidence of recurrence (exceptfor non-melanoma skin cancer, adequately treated cervical carcinoma in situ,superficial bladder carcinoma) during the 5 years prior to randomization. Cancertreated with curative intent for >5 years previously and without evidence ofrecurrence will be allowed.
4. Prior selinexor or another XPO1 inhibitor treatment.
5. Administration of a previous gemcitabine-containing treatment.
6. Any concurrent medical condition or disease (e.g. uncontrolled active hypertension,uncontrolled active diabetes, active systemic infection, etc.) that is likely tointerfere with study procedures.
7. Uncontrolled active infection requiring parenteral antibiotics, antivirals, orantifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylacticantibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
8. Pregnant or breastfeeding females.
9. Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois(25) orMosteller(26) method.
10. Life expectancy of less than 3 months.
11. Major surgery within 4 weeks prior to C1D1.
12. Any active gastrointestinal dysfunction interfering with the patient's ability toswallow tablets, or dysfunction that could interfere with absorption of studytreatment.
13. Inability or unwillingness to take supportive medications such as anti-nausea andanti-anorexia agents as recommended by the NCCN CPGO for antiemesis andanorexia/cachexia (palliative care).
14. Any active, serious psychiatric, medical, or other conditions/situations that, in theopinion of the Investigator, could interfere with treatment, compliance, or theability to give informed consent. 15. Presence of brain or central nervous systemmetastases, unless they are controlled (patients with treated and stable metastasisare eligible)
15. Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible)