a phase 1 study of cx1003 (kanitinib) in patients with advanced solid tumors

Conditions: Advanced Solid Tumor

Summary: cx1003 is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit vascular endothelial growth factor receptor 2 (vegfr2) and hepatocyte growth factor receptor (hgfr/met). this study aimed to evaluate the safety, pharmacokinetics, and antitumor activity of cx1003 in patients with refractory advanced or metastatic solid tumors.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed recurrent or metastatic solid tumors; * at least one measurable lesion (spiral ct scan long diameter ≥10 mm or enlarged lymph node short diameter ≥15 mm by recist 1.1); * documented disease progression after, or refractory to, or intolerant of prior standard or established therapy known to provide clinical benefit for their condition; or documented disease progression within 24 weeks after prior adjuvant/neoadjuvant therapy; * ecog ps ≤1; * expected overall survival≥12 weeks; exclusion criteria: * untreated brain metastases or symptoms of brain metastases cannot be controlled more than 4 weeks; * other kinds of malignancies \[excluding stage ib or lower grade cervical cancer，noninvasive basal cell or squamous cell cancer, breast cancer with complete remission (cr) \> 10 years ,melanoma with cr \> 10 years or other malignant tumors with cr \> 5 years\]; * hematologic, renal, and hepatic function abnormities as defined below: absolute neutrophil count (anc) \ 1.5×the upper limit of normal range(uln) without liver metastases; total bilirubin \> 3×uln with liver metastases; ast, alt, alp \>1.5×uln without liver metastases ; ast, alt, alp \>5×uln with liver metastases; primary hepatocellular carcinoma; hepatic cirrhosis with child-pugh b or c; serum creatinine \>1.5×uln; history of previous nephrotic syndrome; inr or appt \>1.5×uln; presence of hemorrhage (hemoptysis) , thrombosis，or currently receiving treatment with warfarin, aspirin, low molecular weight heparin (lmwh), or any other anti-platelet drugs (aspirin ≤100 mg/d for prophylaxis are allowed); •any of the following gastrointestinal disease: unable to swallow oral drugs; need intravenous nutrition; history of a gastric resection; history of treatment for active peptic ulcer disease within 6 months; clinically significant gastrointestinal bleeding within 3 months; persistent grade 2 or higher chronic diarrhea despite optimal medical management; •any of the following cardiovascular and cerebrovascular disease: myocardial infarction , severe cardiac arrhythmias, unstable angina, coronary artery disease, congestive heart failure, cerebrovascular accident or tia within 12 months ; deep vein thrombosis or pulmonary embolism within 6 months; qtcf \>470 msec; uncontrolled hypertension despite optimal medical management; * presence of unresolved toxicities from prior anticancer therapy, defined as having not resolved to nci ctcae v5.0 grade 0 or 1 with the exception of alopecia; * involved in other clinical trials within 30 days of enrollment; * major surgical procedure, open biopsy, or significant traumatic injury within 30 days of enrollment; * history of organ allograft ; * need glucocorticoids or other immunosuppressive agents for immunosuppression (excluding local or inhaled glucocorticoids); * uncontrolled ongoing or active infection; * known history of human immunodeficiency virus (hiv) infection or current chronic or active hepatitis b or c infection requiring treatment with antiviral therapy; * pregnant or lactating women or those who do not take contraceptives, including men; * suffering from mental and neurological diseases; * any other metabolic dysfunction, abnormal physical examination findings, or clinical laboratory findings; * inability to comply with protocol required procedures.