4006-776-356 出国就医服务电话

免费获得国外相关药品,最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Efficacy and Safety of Anlotinib in Adjuvant Therapy for High-grade Soft Tissue Sarcoma

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

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Adult High Grade Sarcoma Drug: Anlotinib Hydrochloride Drug: Placebo Oral Tablet Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : May 13, 2019
Estimated Primary Completion Date : May 13, 2022
Estimated Study Completion Date : August 13, 2022
Arms and Interventions
Arm Intervention/treatment
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.

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.

Outcome Measures
Primary Outcome Measures :
  1. DFS [ Time Frame: 2 years ]
    Disease Free Survival

  2. 1-year and 2-year DFR [ Time Frame: 2 years ]
    1-year and 2-year disease-free survival rates


Secondary Outcome Measures :
  1. OS [ Time Frame: 2 years ]
    Overall Survival

  2. LRFS [ Time Frame: 2 years ]
    Local Recurrence Free Survival

  3. DMFS [ Time Frame: 2 years ]
    Distant Metastasis Free Survival


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations

Contacts
Layout table for location contacts
Contact: Wangjun Yan, M.D. +86 18121299399 yanwj@fudan.edu.cn
Contact: Chunmeng Wang, M.D. +86 18017317143 cmwang1975@163.com

Locations
Layout table for location information
China, Guangdong
Cancer Hospital of Sun Yat-sen
Guangzhou, Guangdong, China, 510060
Contact: Jing Wang, M.D.         
Sub-Investigator: Jing Wang, M.D.         
China, Yunnan
Yunnan Cancer Hospital
Kunming, Yunnan, China, 650118
China, Zhejiang
Zhengjiang Cancer Hospital
Hangzhou, Zhejiang, China, 310022
Contact: Tao Li, M.D.         
Sub-Investigator: Tao Li, M.D.         
China
Fudan University Shanghai Cancer Center
Shanghai, China, 200032
Contact: Wangjun Yan, M.D.    18121299399    yanwj@fudan.edu.cn   
Contact: Chunmeng Wang, M.D.    18017317143    cmwang1975@163.com   
Principal Investigator: Wangjun Yan, M.D.         
Principal Investigator: Chunmeng Wang, M.D.         
The Six People's Hospital Affiliated to Shanghai Jiao Tong University
Shanghai, China, 200233
Contact: Yang Dong, M.D.         
Sub-Investigator: Yang Dong, M.D.         
Sponsors and Collaborators
Fudan University
Investigators
Layout table for investigator information
Principal Investigator: Wangjun Yan Fudan University
Tracking Information
First Submitted Date  ICMJE May 10, 2019
First Posted Date  ICMJE May 15, 2019
Last Update Posted Date May 15, 2019
Estimated Study Start Date  ICMJE May 13, 2019
Estimated Primary Completion Date May 13, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • DFS [ Time Frame: 2 years ]
    Disease Free Survival
  • 1-year and 2-year DFR [ Time Frame: 2 years ]
    1-year and 2-year disease-free survival rates
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • OS [ Time Frame: 2 years ]
    Overall Survival
  • LRFS [ Time Frame: 2 years ]
    Local Recurrence Free Survival
  • DMFS [ Time Frame: 2 years ]
    Distant Metastasis Free Survival
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Anlotinib in Adjuvant Therapy for High-grade Soft Tissue Sarcoma
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Soft Tissue Sarcoma Adult
  • High Grade Sarcoma
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: Anlotinib Gruop
    Intervention: Drug: Anlotinib Hydrochloride
  • Placebo Comparator: Placebo Group
    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2019)
88
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 13, 2022
Estimated Primary Completion Date May 13, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wangjun Yan, M.D. +86 18121299399 yanwj@fudan.edu.cn
Contact: Chunmeng Wang, M.D. +86 18017317143 cmwang1975@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03951571
Other Study ID Numbers  ICMJE IRB1902197-8
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Wangjun Yan, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wangjun Yan Fudan University
PRS Account Fudan University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院