A Phase 1 Study of CX1003 (Kanitinib) in Patients with Advanced Solid Tumors

Официальное название

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

Обзор

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.

Вмешательства

• Препарат CX1003
  Oral dose A 4-day single dose period, followed by a period of daily-dose in continuous 28-day treatment cycle (the 1st cycle) or 21-day treatment cycles (the 2nd cycle and beyond) Dosage range: 25 mg, 50mg, 75mg, 100mg,125mg,150mg,175mg

Первичные конечные точки

• Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE 5.0: Dose Escalation Stage [Срок оценки: First 5 weeks after initial administration of CX1003]
• Maximum tolerated dose (MTD): Dose Escalation Stage [Срок оценки: First 5 weeks after initial administration of CX1003]

Вторичные конечные точки (11)

• Pharmacokinetics (PK) profile: Cmax [Срок оценки: First 5 weeks after initial administration of CX1003]
• Pharmacokinetics (PK) profile: Tmax [Срок оценки: First 5 weeks after initial administration of CX1003]
• Pharmacokinetics (PK) profile: T1/2 [Срок оценки: First 5 weeks after initial administration of CX1003]
• Pharmacokinetics (PK) profile: AUC [Срок оценки: First 5 weeks after initial administration of CX1003]
• Pharmacokinetics (PK) profile: CL/F [Срок оценки: First 5 weeks after initial administration of CX1003]
• Pharmacokinetics (PK) profile: Vz/F [Срок оценки: First 5 weeks after initial administration of CX1003]
• Objective Response Rate (ORR) [Срок оценки: up to 24 months]
• Progression-free survival (PFS) [Срок оценки: up to 24 months]
• Disease Control Rate (DCR) [Срок оценки: up to 24 months]
• Duration of Response (DOR) [Срок оценки: up to 24 months]
• Safety profile as assessed by the incidence, duration, and severity of adverse events [Срок оценки: From first dose of CX1003 to 30 days after last dose]

Критерии участия

Критерии включения

• 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;

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Uni — Пекин

Идентификаторы

NCT: NCT04093466 · KNTN-I-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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