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.

Study Overview

• Status: Unknown
• Conditions: Soft Tissue Sarcoma Adult; High Grade Sarcoma
• Intervention / Treatment: Drug: Anlotinib Hydrochloride; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wangjun Yan, M.D.; Phone Number: +86 18121299399; Email: yanwj@fudan.edu.cn
• Study Contact Backup: Name: Chunmeng Wang, M.D.; Phone Number: +86 18017317143; Email: cmwang1975@163.com

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
    • Contact: Wangjun Yan, M.D.; Phone Number: 18121299399; Email: yanwj@fudan.edu.cn
    • Contact: Chunmeng Wang, M.D.; Phone Number: 18017317143; Email: cmwang1975@163.com
    • Principal Investigator: Wangjun Yan, M.D.
    • Principal Investigator: Chunmeng Wang, M.D.
  • Shanghai, China, 200233
    • The Six People's Hospital Affiliated to Shanghai Jiao Tong University
    • Contact: Yang Dong, M.D.
    • Sub-Investigator: Yang Dong, M.D.
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Hospital of Sun Yat-sen
      • Contact: Jing Wang, M.D.
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhengjiang Cancer Hospital
      • Contact: Tao Li, M.D.
      • Sub-Investigator: Tao Li, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	Drug: Placebo Oral Tablet; Before breakfast, take an placebo once a day, 1 pill at a time. Continuous oral administration for two weeks and stop for one week. Three weeks (21 days) for a treatment cycle. The total treatment cycles is six.
Experimental: Anlotinib Gruop	Drug: Anlotinib Hydrochloride; Before breakfast, take an Anlotinib hydrochloride placebo once a day, 12 mg (1 pill) at a time. Continuous oral administration for two weeks and stop for one week. Three weeks (21 days) for a treatment cycle. The total treatment cycles is six.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	Disease Free Survival	2 years
1-year and 2-year DFR	1-year and 2-year disease-free survival rates	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	2 years
LRFS	Local Recurrence Free Survival	2 years
DMFS	Distant Metastasis Free Survival	2 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Wangjun Yan, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 13, 2019
• Primary Completion (Anticipated): May 13, 2022
• Study Completion (Anticipated): August 13, 2022

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 14, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: IRB1902197-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No