A Study of Different Dosing Schedules of Selinexor in Sarcoma Patients

Korábbi kezelés

• Has received selinexor or another XPO1 inhibitor previously
• 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.
• Major surgery within 4 weeks before initiation of therapy
• Active, ongoing or uncontrolled active infection within one week prior to first dose
• Concurrent therapy with approved or investigational anticancer therapeutic agents

Más betegség

• 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.
• 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

Egyéb

• Patients who are pregnant or lactating
• 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;
• In the opinion of the Investigator, patients who are significantly below their ideal body weight (Body Surface Area ≤ 1.2m2)

• Written informed consent in accordance with federal, local, and institutional guidelines
• Age > 18 years.
• Patients must have histologically confirmed locally advanced/unresectable or metastatic STS
  • For Arm A the acceptable histologies are MPNST, ESS and LMS
  • For Arm B arm all STS histologies are eligible
• Patients must fall into one of the three following categories:
  • Show evidence of progressive disease on study entry; or
  • Be treatment naïve, but have progressed since diagnosis; or
  • Newly diagnosed patients with de novo metastatic measurable disease.
• Patient must have measureable disease as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate hematopoietic function within 7 days prior to C1D1:
  • absolute neutrophil count (ANC) ≥1.0x109/L
  • hemoglobin ≥ 90 g/L
  • platelet count ≥100 x 109/L
  • 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.
  • Patients must have:
  • At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
  • At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.
  • However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
• Adequate hepatic function within 28 days prior to C1D1:
  • 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)
  • 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;
• 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.
• 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.
• Ability to swallow pills