Phase II Study of Chiauranib Capsule in Advanced or Unresectable Soft Tissue Sarcoma

Soft Tissue Sarcoma Clinical Trial

Official title:

An Open-label, Multicenter, Phase II Study of Chiauranib Capsule in Patients With Advanced or Unresectable Soft Tissue Sarcoma Previously Failed to Standard of Care Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05542433
• Other study ID #: Chiauranib phase II
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2, 2022
• Est. completion date: August 2, 2024

Study information

• Verified date: September 2022
• Source: Sun Yat-sen University
• Contact: Xing Zhang, PhD, MD
• Phone: 86-020-87343192
• Email: zhangxing[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to explore the preliminary efficacy of Chiauranib monotherapy in patients with advanced or unresectable soft tissue sarcoma who failed standard therapy, and the safety of Chiauranib monotherapy in patients with advanced or unresectable soft tissue sarcoma who failed standard therapy and the relationship between potential biomarkers and preliminary efficacy.

Description:

Chiauranib has not yet been approved for marketing at home and abroad. It is a small-molecule anti-tumor targeted drug targeting multiple protein kinases. It has a three-way anti-tumor synergistic mechanism, including anti-tumor angiogenesis, inhibiting tumor cell mitosis, and regulating tumor inflammatory microenvironment, and exerts a comprehensive anti-tumor effect; at the same time, its high target selectivity also reduces the risk of Risk of side effects from off-target effects.

Chiauranib has shown preliminary anti-tumor effects in multiple tumor types clinically, among which, two tumor types, small cell lung cancer and ovarian cancer, have entered phase III clinical studies. Drugs with similar mechanisms of action, pazopanib, regorafenib, anlotinib, apatinib (VEGFR, etc.) and Alisertib (targeting Aurora A, etc.) single-agents have demonstrated certain anti-tumor activity in STS patients , which provides a certain reference for Chiauranib.

The trial used a single-arm, open-label, multicenter design to explore the preliminary efficacy and safety of Chiauranib in patients with advanced or unresectable soft tissue sarcoma who had failed standard therapy. If a subtype or several subtypes are found to have better efficacy, or if the biomarker study suggests a relationship with the initial efficacy, further research in specific subtypes will be considered after discussion between the investigator and the sponsor. The whole experimental study includes three phases: screening period, treatment period and follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2, 2024
• Est. primary completion date: August 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 18-75 years (including cutoff values) when signing the informed consent form, regardless of gender;

• All pathologically diagnosed advanced or unresectable soft tissue sarcomas, standard Treatment failure or no standard treatment regimen, mainly including liposarcoma, leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, fibrosarcoma, clear cell sarcoma, angiosarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, undifferentiated sarcoma, Ewing's sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, myofibroblastic sarcoma, malignant solitary fibroma, post-radiotherapy sarcoma, etc. (except gastrointestinal stromal tumor, etc.). Pathological subtypes without standard treatment options can receive first-line treatment, including but not limited to acinar soft tissue sarcoma, malignant peripheral nerve sheath tumor, clear cell sarcoma, epithelioid sarcoma, well-differentiated/dedifferentiated liposarcoma, post-radiotherapy sarcoma, etc. ;

• According to the RECIST1.1 criteria, there is at least one measurable target lesion, and the lesions of radiotherapy or local area therapy must have imaging evidence of disease progression before they can be regarded as target lesions;

• ECOG physical fitness score 0-1 points;

• The main organ functions meet the following criteria: Blood routine: absolute value of neutrophils = 1.5×109/L, platelets =75×109/L, hemoglobin = 80 g/L (not allowed within 14 days before the first medication); Blood biochemistry: serum creatinine (Cr)=1.5×Upper limit of normal (ULN); total bilirubin=1.5×ULN, AST, ALT=2.5× ULN (=5×ULN if liver metastases); Coagulation function: International Normalized Ratio (INR) < 1.5 (anticoagulation therapy is not allowed within 14 days before the first dose, except for prophylactic anticoagulation therapy at a stable dose).

• Expected survival time = 3 months; 7. Voluntary signed written informed consent.

Exclusion Criteria:

• Active central nervous system (CNS) symptoms during the screening period and/or CNS metastases requiring hormone therapy within 28 days before the first dose, or lesions involving the brainstem or pia mater;

• Screening patients whose tumor has invaded around important blood vessels by imaging at the early stage or the investigators judged that the tumor is very likely to invade important blood vessels and cause massive hemorrhage;

• Patients with clinical symptoms or pleural effusion, ascites, and pericardial effusion that need to be drained during the screening period;

• Currently or in the past with other malignant tumors (except for adequately treated basal cell carcinoma of the skin or squamous cell carcinoma, carcinoma in situ of the cervix), unless radical treatment has been performed and there is no evidence of recurrence and metastasis within the past 5 years;

• Received aurora kinase inhibitor or VEGF/VEGFR inhibitor therapy in the past such as sunitinib, bevacizumab, apatinib, endo, pazopanib, regorafenib, lenvatinib, etc. ( for patients who are suitable for anlotinib treatment, only those who cannot receive anlotinib for various reasons are allowed to be enrolled in this study, and patients who have received anlotinib in the past are prohibited from entering this study);

• First-time medication: Those who have used anti-tumor therapy such as radiation therapy, chemotherapy, immunotherapy, and targeted therapy within the previous 28 days;

• Those who are allergic to any component or excipient of the test drug or have contraindications;

• Those who have used it within 28 days before the first drug use Investigational drugs or devices;

• Major surgical operations (such as craniotomy, thoracotomy or laparotomy) or severe unhealed wounds, ulcers or fractures, etc. have been received within 28 days before the first drug use;

• Screening period The original treatment toxicity has not been recovered, and there are still toxic reactions above grade 1 (except for alopecia) that meet the criteria of CTCAE 5.0;

• There are uncontrolled or important cardiovascular diseases, including: 6 times before the first administration of the study drug New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, myocardial infarction, or arrhythmias requiring treatment at screening within one month, and left ventricular ejection fraction (LVEF) <50%; History of primary cardiomyopathy (eg, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy); Clinically significant QTc interval prolongation medical history, or QTc interval >470ms in women and >450ms in men during the screening period; Symptomatic coronary heart disease requiring drug treatment during the screening period; Concurrent use of =3 antihypertensive drug components within 14 days before the first dose treatment records, or systolic blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg during the screening period (at rest, with an interval of about 5 minutes, three consecutive measurements, and the average value); Hypertension has occurred in the past crisis or hypertensive encephalopathy; During the screening period, there are other patients who are judged by the investigator to be unsuitable for inclusion. Cardiovascular diseases.

• Presence of interstitial lung disease or pulmonary fibrosis or pulmonary inflammation requiring treatment on chest imaging during the screening period, or a history of pneumonitis receiving oral or intravenous steroids within 6 months prior to the first dose;

• The screening period: there are obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of the drug (such as inability to swallow, chronic diarrhea, intestinal obstruction, after small bowel resection, etc.), or total gastrectomy, or before the first drug History of gastrointestinal perforation and/or fistula within 6 months;

• 24-hour urine protein quantitative test must be performed when urine protein is =2+ in routine urine examination during the screening period;

• Active bleeding within 2 months before the first medication, or taking anticoagulant drugs during the screening period (such as warfarin, phenylpro- coumarin, low-dose aspirin, low-molecular-weight heparin, etc.), or during the screening period, the investigator judged that there is a high risk of bleeding (such as esophageal and gastric varices with bleeding risk, locally active ulcer lesions, positive fecal occult blood cannot rule out gastrointestinal bleeding, intermittent hemoptysis, etc.);

• Before the first medication 6 Thrombotic events such as deep vein thrombosis or pulmonary embolism or cerebrovascular accident (implantable venous infusion port or catheter-derived thrombosis, which will be evaluated by the investigator to determine whether it can be enrolled) within one month;

• Systemic need for systemic Active infection for treatment (oral, intravenous infusion);

• HIV antibody positive screening test;

• Screening test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with positive viral replication, hepatitis C antibody (HCV- Ab) positive with virus replication positive. (Note: qualitative testing is preferred, and quantitative testing for viral replication when needed);

• Any mental or cognitive impairment that may limit the understanding, execution of informed consent, and compliance with research;

• Long-term drug meditation;

• Pregnant or lactating women; women of childbearing age who are unwilling or unable to use effective methods of contraception during the entire treatment period of this trial and within 12 weeks after the last dose of the trial [Women of childbearing age include: Any menarche without successful artificial sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or nonmenopausal]; if the partner is a woman of childbearing age, the subject is not using effective contraception;

• The investigator believes that other conditions that are not suitable to participate in this trial, such as concomitant diseases, concomitant treatment or any abnormal laboratory tests, may interfere with the evaluation of the efficacy and safety results of the trial.

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• Chiauranib
All subjects were treated with Chiauranib capsules, 50 mg (2 capsules), orally every morning on an empty stomach, once a day, continuously. The drug was taken until tumor progression, death, unacceptable toxicity, withdrawal of informed consent, loss to follow-up, or the end of the trial (whichever occurred first).

Locations

Country	Name	City	State
China	Sun Yat-Sen Univerisity	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Shenzhen Chipscreen Biosciences Co.Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gene alterations/protein expression	Exploring gene alterations or protein expression related with PFR 12w, ORR, PFS, etc.	270 days
Primary	Progression-free survival rate at 12 weeks (PFR 12w)	The proportion of subjects who did not experience disease progression or relapse (according to RECIST 1.1 criteria) or death from any cause at 12 weeks after receiving the drug.	84 days
Secondary	Objective response rate (ORR)	According to the RECIST1.1 criteria, the sum of subjects with complete response (CR) and partial response (PR) in response to efficacy accounted for the proportion of the total population in the analysis set.	270 days
Secondary	Progression-free survival (PFS)	The length of time from the first drug to the occurrence of disease progression or relapse (according to RECIST1.1 criteria) or death from any cause (whichever occurs first). PFS data were collected until the end of the trial as specified in this protocol.	270 days
Secondary	Disease control rate (DCR)	According to RECIST1.1 criteria, the proportion of subjects who achieved CR, PR and SD (at least at the planned first efficacy assessment) The proportion of the total number of people in the analysis set.	270 days
Secondary	Overall survival (OS)	The time from the first medication to death from any cause. OS data were collected until the end of the trial as specified in this protocol.	270 days
Secondary	Number of participants with abnormal laboratory values and/or adverse events that are related to treatment	Frequency and severity of adverse events, changes in various vital signs, physical examination and laboratory indicators. The severity of adverse events was judged according to CTCAE 5.0 criteria.	270 days