Anlotinib Combined With Toripalimab in Refractory and Advanced Soft-tissue Sarcoma

NCT04172805 | Unknown Phase 2

• 1 other identifier: SunYat-senU-anlotinib &pd-1
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Soft tissue sarcoma (STS) is a relatively rare type of malignant tumor with an incidence of 1-2/100000. For unresectable or widely disseminated advanced STS, a combined clinical trial is the best way to obtain evidence-based medical evidence. Anlotinib, a multi-target receptor tyrosine kinase inhibitor (TKI), is effective for various histological types of STS and the safety is tolerable. TKIs may reverse drug resistance or inefficiency of immunoassay inhibitors, and combination therapy has shown preliminary efficacy in a variety of tumors. Because of the poor prognosis of refractory and advanced STS, there is no standard second-line treatment. Therefore, combined therapies based on the original targeted drugs would be paid more concentrations in the future. We focus on exploring the feasibility of combination of anlotinib and Toripalimab monoclonal antibody in advanced, refractory and progressive soft tissue sarcoma after failure of standard treatment, and look forward to further improving the efficacy of soft tissue sarcoma.

Conditions

Sarcoma,Soft Tissue

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.

  Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)

Secondary Outcomes (3)

• Progress free survival

  Time Frame: until Progressive Disease (PD) or death (up to 24 months)

• Overall Survival

  Time Frame: From randomization until death (up to 24 months)

• Disease Control Rate

  Time Frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)

Study Arms (1)

anlotinib combined with Toripalimab

EXPERIMENTAL

Anlotinib 12mg orally per day, two weeks on , one week off; 240 mg of toripalimab (fixed dose) every three weeks.

Drug: anlotinib and toripalimab

Interventions

anlotinib and toripalimab DRUG

Anlotinib 12mg orally per day, two weeks on , one week off; 240 mg of toripalimab (fixed dose) every three weeks. Repeat every three weeks. Patients with disease control (CR + PR + SD) and tolerable adverse reactions continued to take medication until the researchers concluded that patients were not suitable to continue medication or the efficacy evaluation was disease progression (PD). No other antineoplastic treatment can be given during the treatment.

Also known as: Anlotinib Hydrochloride

anlotinib combined with Toripalimab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily joined the study and signed informed consent, with good adherence and follow-up.
• Male or female patients aged 18-70 years, ECOG PS score: 0 to 2 points; expected survival over 3 months.
• All advanced soft tissue sarcomas, first-line treatment failure or inability to tolerate first-line treatment, diagnosed by histology, at least one measurable lesion according to RECIST 1.1, including synovial sarcoma, leiomyosarcoma, alveolar soft tissue sarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, liposarcoma, fibrosarcoma, clear cell sarcoma, angiosarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, undifferentiated sarcoma, dermatofibrosarcoma, inflammatory myofibroblast sarcoma, malignant solitary fibroids. However, the following types can be treated first-line: alveolar soft tissue sarcoma, well differentiated / dedifferentiated / pleomorphic liposarcoma, clear cell sarcoma;
• At least one target lesion measurable according to RECIST version 1.1 in the past 3 months, and in at least 1 direction (maximum diameter required to be recorded) can be obtained by magnetic resonance imaging (MRI) or computed tomography (CT) Accurate measurement, where conventional CT ≥ 20 mm or ≥ 10 mm under spiral CT.
• The main organ function meets the following criteria within 7 days of treatment:
• Blood routine examination criteria (without blood transfusion within 14 days): hemoglobin (HB) ≥ 90g / L; neutrophil absolute value (ANC) ≥ 1.5 × 109 / L; platelets (PLT) ≥ 80 × 109 / L.
• Biochemical tests are subject to the following criteria: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5ULN, such as with liver metastasis, then ALT and AST ≤ 5ULN; serum creatinine (Cr) ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min;
• Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low (50%).
• Women of childbearing age must have taken reliable contraceptive measures and performed a pregnancy test (serum or urine) within 7 days prior to enrollment, and the results were negative, and were willing to use appropriate methods during the trial and 8 weeks after the last administration of the test drug. For men, consent must be given to the appropriate method of contraception or surgical sterilization during the trial and 8 weeks after the last administration of the test drug.

You may not qualify if:

• Patients who have previously been treated with anlotinib or anti-PD-1/PD-L1 antibodies.
• Exceeded or currently suffering from other malignant tumors within 5 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (in situ carcinoma) And T1 (tumor infiltrating basement membrane)\].
• Planning to use cytotoxic therapy, signal transduction inhibitors, immunotherapy (or mitomycin C used within 6 weeks prior to receiving the test drug) within 4 weeks prior to enrollment or during the study. Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks prior to enrollment or limited-field radiotherapy to be evaluated for tumor lesions within 2 weeks prior to grouping.
• Hair loss is not included due to unresolved toxicities above CTC AE Level 1 for any prior treatment.
• A variety of factors that affect oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction), and symptomatic treatment is uncontrollable.
• With pleural effusion or ascites, causing respiratory syndrome (≥ CTC AE grade 2 dyspnea \[level 2 dyspnea refers to short-term shortness of activity; affecting instrumental activities of daily living\]), and symptomatic treatment is uncontrollable.
• Active central nervous system (CNS) metastases with clinical signs including cerebral edema, steroid requirements, or progressive disease. Patients with previously treated brain or meningeal metastases must be clinically stable (magnetic resonance imaging \[MRI\] shows no evidence of new or enlarged metastases at least 4 weeks apart) and stop the immunosuppressant amount of systemic steroids (\> 10 Mg / day) prednisone or equivalent) at least 2 weeks prior to study drug administration.
• Patients with abnormal thyroid function after optimal drug treatment.
• Patients with any severe and/or uncontrolled diseases, including:
• Hypertension and uncontrollable levels of normal anti-hypertensive medication (within 3 months): systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg.
• Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months prior to enrollment, unstable or severe angina, or coronary artery bypass surgery, congestive heart failure (New York Heart Association (NYHA) ) \> 2), ventricular arrhythmia requires medical intervention, left ventricular ejection fraction (LVEF) \<50%. Have grade I or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTC ≥ 480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification);
• Active or uncontrolled serious infection (≥ CTC AE Level 2 infection);
• Objective evidence of previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impaired lung function, etc.
• Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral therapy;
• Renal failure requires hemodialysis or peritoneal dialysis;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Xing Zhang

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

anlotinib; toripalimab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xing Zhang

CONTACT

020-87343383; zhangxing@sysucc.org.cn

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: Vice director of department of medical sarcoma and melanoma,Principal Investigator,Clinical Professor

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 21, 2019
• Study Start: March 13, 2020
• Primary Completion: March 1, 2024
• Study Completion: May 15, 2024
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (1)