Anlotinib Hydrochloride Combined With Liposomal Doxorubicin in the Treatment of Locally Advanced or Metastatic Soft Tissue Sarcoma

NCT03880695 | Unknown Phase 2

• 1 other identifier: 2018PHD008-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

Brief Summary

The investigators explored the activity of anlotinib combined with Liposomal Doxorubicin in patients with Locally Advanced or Metastatic Soft Tissue Sarcoma

Conditions

Sarcoma

Outcome Measures

Primary Outcomes (1)

• Progress free survival (PFS)

  Calculated from the date of treatment start until last follow-up or death, whichever comes first.

  each 42 days to evaluate up to intolerance the toxicity or PD (in first 24 weeks), each 84 days to evaluate up to intolerance the toxicity or PD (up to 24 months)

Secondary Outcomes (4)

• Overall Survival (OS)

  From randomization until death (up to 24 months)

• Objective Response Rate (ORR)

  each 42 days to evaluate up to intolerance the toxicity or PD (in first 24 weeks), each 84 days to evaluate up to intolerance the toxicity or PD (up to 24 months)

• Disease Control Rate (DCR)

  each 42 days to evaluate up to intolerance the toxicity or PD (in first 24 weeks), each 84 days to evaluate up to intolerance the toxicity or PD (up to 24 months)

• Quality of Life (QoL)

  each 42 days to evaluate up to intolerance the toxicity or PD (in first 24 weeks), each 84 days to evaluate up to intolerance the toxicity or PD (up to 24 months)

Study Arms (1)

Anlotinib+ Liposomal Doxorubicin

EXPERIMENTAL

Anlotinib Hydrochloride Combined With Liposomal Doxorubicin Liposomal Doxorubicin 50mg/m2 Day 1 every-3-weeks (Q3W) and Anlotinib 12mg QD po at Day 8-21 Q3W and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent. Dose reductions/modifications will be applied as indicated by toxicities and/or patient tolerance.

Drug: Anlotinib+ Liposomal Doxorubicin

Interventions

Anlotinib+ Liposomal Doxorubicin DRUG

Anlotinib : 12 mg, qd, po day 8-21 every 3 weeks Liposomal Doxorubicin: 50 mg/m2, day 1 every 3 weeks

Also known as: Anlotinib+ LPD

Anlotinib+ Liposomal Doxorubicin

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed the informed consent form prior to patient entry;
• ≥ 14 years of age , regardless of gender；ECOG :0-1;Expected Survival Time: Over 3 months;
• Histologically confirmed diagnosis of un-resectable or recurrent metastatic soft tissue sarcoma, such as: leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, liposarcoma , angiosarcoma, alveolar soft tissue sarcoma, and other sarcomas. The following histologies are excluded: embryonic rhabdomyosarcoma, chondrosarcoma, osteosarcoma, gastrointestinal stromal tumor and Ewing sarcoma/primary neuroectodermal tumor.
• Previously without anthracyclines or other anti-tumor drugs
• Evaluable disease by imaging or physical exam or measurable disease defined as at least one lesion that can be accurately measured according to RECIST version 1.1.
• Normal main organs function as defined below: Hemoglobin (Hb) ≥ 80g / L, Neutrophils (ANC) ≥ 1.5 × 10\^9 / L, Platelet count (PLT) ≥ 80 × 10\^9 / L, Serum creatinine (Cr) ≤ 1.5 × normal upper limit (ULN) or creatinine clearance (CCr) ≥ 60ml / min, Blood urea nitrogen (BUN) ≤ 2.5 × normal upper limit (ULN); Total bilirubin (TB) ≤ 1.5 × ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; If accompanied by liver metastases, ALT and AST ≤ 5 × ULN Albumin (ALB) ≥ 25 g/L. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%)
• Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped.

You may not qualify if:

• Prior treatment with anlotinib or any other VEGFR tyrosine kinase inhibitor (such as sunitinib, sorafenib, bevacizumab, imatinib, famitinib, apatinib, regorafenib and other drugs).
• Systemic anti-tumor therapy, including cytotoxic therapy, signal transduction inhibitors, and immunotherapy, is planned for the first 4 weeks prior to enrollment or during the study. Radiation radiotherapy (EF-RT) was performed within 4 weeks prior to enrollment.
• A history of other malignancy ≤ 3 years previous
• Known central nervous system metastases.
• Imaging (CT or MRI) shows tumor lesions from large vessels ≤ 5 mm, the tumor is very likely to invade the important blood vessels and cause fatal hemorrhage, or the formation of tumor thrombosis with large veins (iliac vessels, inferior vena cava, pulmonary veins, superior vena cava);
• The investigator judged that the presence of distinct pulmonary cavitary or necrotic tumors;
• Serosal effusion with clinical symptoms requiring surgical management (including hydrothorax and ascites pericardial effusion)
• With uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite optimal drug treatment).
• Arrhythmias with grade II and above myocardial ischemia or myocardial infarction, poor control (including corrected QT interval(QTc) men ≥ 450 ms, women ≥ 470 ms).
• According to NYHA criteria, grade III to IV cardiac insufficiency, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) \<50%, myocardial infarction occurred within 6 months before enrollment, ≥ 2 congestive heart failure (New York Heart Association ( NYHA) rating ), uncontrolled angina, clinical pericardial disease, or electrocardiogram suggesting acute ischemia or active conduction system abnormalities.
• Uncontrolled comorbid diseases, including but not limited to: poorly controlled diabetes, persistent active infections, or mental illness or social condition that may affect a subject's adherence to the study.
• Patients with active hepatitis B or hepatitis C (hepatitis B: HBsAg-positive and hepatitis B virus(HBV) DNA ≥ 500 IU/mL; hepatitis C: hepatitis C virus(HCV) RNA-positive and abnormal liver function), or active infection requiring antimicrobial treatment (eg Treated with antibacterial drugs, antiviral drugs, antifungal drugs)
• Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0 g;
• Patients with seizures and need treatment
• Abnormal coagulation (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or activated partial thromboplastin time(APTT) \> 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Peking University Shougang Hospital: collaborator
• Peking University Cancer Hospital & Institute: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator
• The First Hospital of Jilin University: collaborator
• Hunan Cancer Hospital: collaborator
• Ruijin Hospital: collaborator
• Liaoning Cancer Hospital & Institute: collaborator

Study Sites (8)

Peking University Shougang Hospital

Beijing, Beijing Municipality, 100034, China

NOT YET RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

NOT YET RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

NOT YET RECRUITING

First Hospital of Jilin University

Changchun, Jilin, China

NOT YET RECRUITING

Liaoning Tumor Hospital & Institute

Shenyang, Liaoning, China

NOT YET RECRUITING

Ruijin Hospital

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

NOT YET RECRUITING

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Wei Guo, MD

CONTACT

+86-13701195504; bonetumor@163.com

Xin Sun

CONTACT

+86-10-66583761

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 19, 2019
• Study Start: March 1, 2019
• Primary Completion: April 1, 2021
• Study Completion: May 1, 2021
• Last Updated: March 21, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)