A Multicenter, Open-label, Single-arm Study of Surufatinib in Combination With Tislelizumab for Second-line and Further Treatment of Metastatic Triple-negative Breast Cancer (TNBC)

Huihua Xiong1 site in 1 country45 target enrollmentApril 2023

ConditionsMetastatic Triple-negative Breast Cancer

InterventionsSurufatinib Tislelizumab

DrugsSurufatinib Tislelizumab

Overview

Phase: Phase 1
Intervention: Surufatinib
Conditions: Metastatic Triple-negative Breast Cancer
Sponsor: Huihua Xiong
Enrollment: 45
Locations: 1
Primary Endpoint: Progression-free survival
Status: Not Yet Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter, open-label, single-arm clinical study designed to evaluate the safety and efficacy of surufatinib combined with tislelizumab in the treatment of metastatic triple-negative breast cancer (TNBC). The study will be conducted in two parts; Safety lead-in phase and dose expansion phase.

Registry

clinicaltrials.gov

Start Date

April 2023

End Date

August 2025

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Huihua Xiong

Responsible Party

Sponsor Investigator

Principal Investigator

Huihua Xiong

Chief physician

Tongji Hospital

Eligibility Criteria

Inclusion Criteria

•Patients voluntarily participated in the study, signed the informed consent, and had good compliance;
•Female patients ≥18 years;
•TNBC confirmed by histology or cytology. Triple negative is defined as \<1% expression of estrogen receptor (ER) and progesterone receptor (PR), and negative in situ hybridization expression of human epidermal growth factor receptor 2 (HER2).
•Unresectable locally advanced or metastatic TNBC failed or relapsed after treatment with at least one line of standard chemotherapy regimens (taxanes and/or anthracyclines). For patients with documented germ line BRCA1/BRCA2 (breast cancer 1 gene/breast cancer 2 gene) mutations, PARP inhibitors can be considered as one of the previous standard therapies if they have been treated with approved PARP inhibitors;
•Patients should have at least one measurable lesion (RECIST 1.1);
•ECOG PS 0 or 1;
•Expected survival ≥12 weeks;
•Blood test (without blood transfusion within 14 days)
•Neutrophil absolute value ≥1.5×109/L, platelet ≥100×109/L, hemoglobin concentration ≥9g/dL);
•Liver function test (aspartate aminotransferase and glutamic aminotransferase ≤2.5×ULN, bilirubin ≤1.5×ULN; In the presence of liver metastasis, AST and ALT≤5×ULN);

Exclusion Criteria

•During the first 4 weeks of treatment, receive the following treatments: including but not limited to surgery, chemotherapy, radical radiotherapy, biotargeted therapy, immunotherapy, and other investigational drugs;
•Previous treatment with anti-VEGF /VEGFR targeting drugs, such as Surufatinib; Or have previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or synergistic inhibition of T cell receptors in response to another stimulus (including but not limited to CTLA-4, OX-40, LAG-3, CD137, etc.);
•Immunosuppressive drugs have been administered in the 14 days prior to initiation of treatment, but do not include nasal and inhaled corticosteroid hormones or physiological doses of systemic steroid hormones (i.e., the daily dose of prednisolone does not exceed 10 mg or the equivalent physiological dose of another corticosteroid);
•History of any active autoimmune disease or autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subjects with vitiligo or asthma may have complete remission in childhood and do not currently require medical intervention, or have a history of allotransplantation or allohematopoietic stem cell transplantation);
•Symptomatic brain or meningeal metastases (except those with brain metastases that have undergone local radiotherapy or surgery for more than 6 months and whose disease control is stable);
•Severe infection (e.g. intravenous antibiotic, antifungal, or antiviral) within 4 weeks of treatment, or unexplained fever \> 38.5 ℃ during screening/initial administration;
•Have high blood pressure that is not well controlled by antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)
•Urine routine indicated urine protein ≥2+, and 24 hours urine protein quantity \>1.0g;
•Obvious clinical bleeding symptoms or obvious bleeding tendency (bleeding \> 30 mL within 3 months, hematemesis, black feces, blood in stool), hemoptysis (fresh blood \> 5 mL within 4 weeks) within 3 months prior to treatment. Or treatment of venous/venous thrombosis events occurring within the preceding 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required;
•Active heart disease, including myocardial infarction, severe/unstable angina, occurs 6 months before treatment. Left ventricular ejection fraction \< 50% by echocardiography and poor arrhythmia control (including QTcF interval, \> 450 ms in men and \> 470 ms in women);

Arms & Interventions

surufatinib + tislelizumab

Safety Lead-in Phase: Six patients with metastatic triple-negative breast cancer will be recruited to receive surufatinib in combination with tislelizumab, and DLT will be evaluated over a 28-day DLT observation period. Dose expansion phase: Surufatinib was administered according to the dose determined in the safety run-in phase and tislelizumab is same as Safety Lead-in Phase.

Intervention: Surufatinib