Efficacy and Safety of Anlotinib in Adjuvant Therapy for High-grade Soft Tissue Sarcoma

Efficacy and Safety of Anlotinib Hydrochloride (AL3818) in Postoperative Adjuvant Therapy for High-grade Soft Tissue Sarcoma -- A Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Clinical Trail

To evaluate the efficacy and safety of Anlotinib Hydrochloride Capsule combined with Best Supportive Therapy in the adjuvant treatment of patients with high-grade soft tissue sarcoma after operation, as compared with placebo combined with Best Supportive Therapy.

Inclusion Criteria:

• 1.High-grade soft tissue sarcoma patients without standard adjuvant chemotherapy after surgery. Mainly includes: liposarcoma(except for Myxoid/round cell liposarcoma), leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, clear cell sarcoma, alveolar soft part sarcoma, angiosarcoma, epithelioid sarcoma, malignant solitary fibrous tumor and so on. Except for rhabdomyosarcoma, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, Ewing sarcoma/primary neuroectodermal tumors, inflammatory myofibroblastoma, malignant mesothelioma.

  2.The postoperative microscopic margin was negative and the pathological diagnosis was high-grade soft tissue sarcoma. The diagnosis was completed by pathologists, and the pathological specimens were confirmed by the research center.

  3.The age is ≥18 years old, the ECOG score is ≤2, and the estimated survival time is more than 3 months.

  4.Examinations meet the following criteria:

  1. Blood routine examination: HB ≥ 100g/L(no blood transfusion within 14 days); ANC ≥ 1.5×10^9 /L; PLT ≥ 80×10^9 /L
  2. Other examinations: Cr ≤ upper limit of normal value (ULN); BIL ≤ ULN; ALTAST ≤ 1.5 × ULN (for patients with liver metastasis ≤ 5 × ULN); fasting triglyceride ≤3.0mmol/L; fasting cholesterol ≤7.75mmol/L;
  3. Doppler ultrasound assessment: LVEF ≥ 50%. 5. Females should agree to use contraceptives (such as intrauterine devices (IUD), birth control pills or condoms) during the study period and 6 months after the end of study and the serum or urine pregnancy test was negative within 7 days prior to study enrollment and must be non-lactating; Males should agree to use contraception during the study period and within six months after the end of the study period.

  6.Patients should participate in the study involuntarily, sign the informed consent, and have good compliant and agree to be followed up.

Exclusion Criteria:

• 1. Patients who have received targeted therapy of vascular endothelial growth inhibitors, such as sunitinib, sorafenib, bevacizumab, imatinib, famitinib and apatinib, etc.

  2. Patients who have malignant tumors previously or concomitantly, except for cured skin basal cell carcinoma and cervical carcinoma in situ; 3. Those who participated in other drug clinical trials within 4 weeks; 4. Those who received chemotherapy within 4 weeks. 5. Those who received anticancer therapy previously and have toxic reactions of NCI-CTC AE grade > grade 1 now; 6. Patients who have multiple factors affecting oral medication (such as inability to swallow, Post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.); 7. Patients who have brain metastases, spinal cord compression, cancerous meningitis, or screening CT or MRI findings of brain or pia mater disease.

  8. Patients have any serious or uncontrolled disease, such as:

  1. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmia; patients with unsatisfactory blood pressure control (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
  2. Active or uncontrolled severe infections;
  3. Liver diseases such as cirrhosis, decompensated liver disease and chronic active hepatitis;
  4. Poor control of diabetes mellitus (FBG > 10mmol/L);
  5. Urinary routine examination showed that urinary protein (++) and confirmed by the 24-hour urinary protein quantification(>1.0 g); 9. Long-term unhealed wound or fracture 10. Patients with bleeding tendency (e.g. active gastrointestinal ulcer) or treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues.

  11. Arterial or venous thrombosis occurred before the first dose, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism.

  12. Those who have a history of psychotropic drug abuse and are unable to get rid of or have mental disorders.

  13. Those who have a history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disorders, or organ transplantation.

  14. According to the investigator's assessment, there are serious concomitant diseases that endanger the safety of the patient or affect the patient's completion of the study.