Lenvatinib and Eribulin in Advanced Soft Tissue Sarcoma

Prior treatment

• Patients who had received lenvatinib or eribulin treatment
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment.

Other illness

• Patients with uncontrollable hypertension (defined as systolic blood pressure over 140mmHg and/or diastolic pressure over 90mmHg despite anti-hypertensive medications)
• Bleeding subjects at risk for severe hemorrhage.
• Arterial thromboembolic event within the past 6 months, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction.
• History of allergic reaction to compounds of similar chemical composition to the study drugs

Lab values

• Patients with the following cardiac disease
  • Prolongation of corrected QT (QTc) interval to \>480 milliseconds (ms).
  • Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II; (b) unstable angina; (c) myocardial infarction; (d) stroke; or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs.

Other

• Patients who had leptomeningeal metastasis, either diagnosed by brain imaging study or confirmed by cerebrospinal fluid cytology examination (patients with brain metastasis that are under control is eligible).
• Patients with clinical signs or symptoms of gastrointestinal obstruction and who require parenteral hydration and/or nutrition because of obstruction.
• Pregnancy or lactation.

• A histological confirmed adipocytic sarcoma (dedifferentiated, myxoid, or pleomorphic) or leiomyosarcoma that is either inoperable locally advanced or metastatic
• Advanced adipocytic sarcoma and leiomyosarcoma who have received no more than 2 lines of systemic chemotherapy in the advanced setting (not including adjuvant chemotherapy).
• At least one measurable tumor according to RECIST 1.1. If the measurable lesion has previously received radiotherapy, the tumor must be a progressive lesion after radiotherapy.
• ECOG PS 0 or 1 or Karnofsky performance status (KPS) ≥ 70
• Patients must have adequate organ function and marrow reserve measured within 14 days prior to randomization as defined below:
  • Hemoglobin ≥ 9.0 g/dL;
  • Absolute neutrophil count ≥ 1,500 /µL;
  • Platelets ≥ 75,000/µL;
  • Total bilirubin ≤ 1.5 x upper normal limit;
  • aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit; for patients with liver metastases AST(SGOT)/ALT(SGPT) ≤ 5 x upper normal limit is allowed;
  • Serum creatinine ≤ 1.5mg/dL or creatinine clearance ≥ 50ml/min;
  • activated partial thromboplastin time (aPTT) \< 1.5 x upper normal limit (unless on therapeutic anti-coagulation);
  • Proteinuria ≤ 1+ with urine dipstick, if \> 1+, 24-hour urine protein must be ≤ 1 g
• Age 20 or older.
• Patient's life expectancy is more than 3 months
• All women of childbearing potential must have a negative pregnancy test obtained within 72 hours before starting therapy.
• Patients with reproductive potential must use effective contraception (hormone or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the completion of therapy.
• Patient needs to have adequate wash-out period from previous systemic treatment(s):
  • (1) 2 weeks for any other oral anti-cancer targeted agents (2) 3 weeks for any other cytotoxic chemotherapy (except for mitomycin-C, which will require 6 weeks) (3) 3 weeks for monoclonal antibodies, including immune checkpoint inhibitors