Clinical trial NCT04093466: A Phase 1 Study of CX1003 (Kanitinib) in Patients with Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Open-label, Dose Escalation/expansion Study Evaluating the Safety, Pharmacokinetics and Preliminary Efficacy of CX1003 (Kanitinib) in the Patients with Relapsed Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Beijing Konruns Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Chinese Academy of Medical Sciences
name: West China Hospital
name: Beijing Tongren Hospital
First posted: 2019-09-18
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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) \<1.5×109 /L or platelet \<100×109 /L or hemoglobin \<9 g/dL; Total bilirubin \> 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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE 5.0: Dose Escalation Stage
timeFrame: First 5 weeks after initial administration of CX1003
measure: Maximum tolerated dose (MTD): Dose Escalation Stage
timeFrame: First 5 weeks after initial administration of CX1003
Secondary outcomes:
measure: Pharmacokinetics (PK) profile: Cmax
timeFrame: First 5 weeks after initial administration of CX1003
measure: Pharmacokinetics (PK) profile: Tmax
timeFrame: First 5 weeks after initial administration of CX1003
measure: Pharmacokinetics (PK) profile: T1/2
timeFrame: First 5 weeks after initial administration of CX1003
measure: Pharmacokinetics (PK) profile: AUC
timeFrame: First 5 weeks after initial administration of CX1003
measure: Pharmacokinetics (PK) profile: CL/F
timeFrame: First 5 weeks after initial administration of CX1003
measure: Pharmacokinetics (PK) profile: Vz/F
timeFrame: First 5 weeks after initial administration of CX1003
measure: Objective Response Rate (ORR)
timeFrame: up to 24 months
measure: Progression-free survival (PFS)
timeFrame: up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: up to 24 months
measure: Duration of Response (DOR)
timeFrame: up to 24 months
measure: Safety profile as assessed by the incidence, duration, and severity of adverse events
timeFrame: From first dose of CX1003 to 30 days after last dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, Doctor
role: PRINCIPAL_INVESTIGATOR
References: