Dataset Information

Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study.

ABSTRACT: Sulfatinib is a small molecule kinase inhibitor that targets tumor angiogenesis and immune modulation. This phase I study (NCT02133157) investigated the safety, pharmacokinetic characteristics, and preliminary anti-tumor activity of sulfatinib in patients with advanced solid tumors. The study included a dose-escalation phase (50-350 mg/day, 28-day cycle) with a Fibonacci (3+3) design, and a tumor-specific expansion phase investigating the tumor response to treatment. Two sulfatinib formulations were assessed: formulation 1 (5, 25, and 50 mg capsules) and formulation 2 (50 and 200 mg capsules). Seventy-seven Chinese patients received oral sulfatinib; the maximum tolerated dose was not reached. Dose-limiting toxicities included abnormal hepatic function and coagulation tests, and upper gastrointestinal hemorrhage. The most common treatment-related adverse events were proteinuria, hypertension and diarrhea. Among 34 patients receiving sulfatinib formulation 2, one patient with hepatocellular carcinoma and eight with neuroendocrine tumors exhibited a partial response; 15 had stable disease. The objective response rate was 26.5% (9/34) and the disease control rate was 70.6% (24/34). Pharmacokinetic, safety, and efficacy data supported continuous oral administration of sulfatinib at 300 mg as the recommended phase II dose. Sulfatinib exhibited an acceptable safety profile and encouraging antitumor activity in patients with advanced solid tumors, particularly neuroendocrine tumors.

SUBMITTER: Xu JM

PROVIDER: S-EPMC5522050 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study.

Xu Jian Ming JM Wang Yan Y Chen Yu Ling YL Jia Ru R Li Jie J Gong Ji Fang JF Li Jing J Qi Chuan C Hua Ye Y Tan Cui Rong CR Wang Jian J Li Ke K Sai Yang Y Zhou Feng F Ren Yong Xin YX Qing Wei Guo WG Jia Hong H Su Wei Guo WG Shen Lin L

Oncotarget 20170601 26

Sulfatinib is a small molecule kinase inhibitor that targets tumor angiogenesis and immune modulation. This phase I study (NCT02133157) investigated the safety, pharmacokinetic characteristics, and preliminary anti-tumor activity of sulfatinib in patients with advanced solid tumors. The study included a dose-escalation phase (50-350 mg/day, 28-day cycle) with a Fibonacci (3+3) design, and a tumor-specific expansion phase investigating the tumor response to treatment. Two sulfatinib formulations ...[more]

PMID: 28159938

Similar Datasets

Project description:BackgroundAST1306 is an orally active irreversible small molecule inhibitor of EGFR (erbB1), HER2 (erbB2) and HER4 (erbB4) signaling. This is a phase I, open-label, dose-escalation study to evaluate the safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor effects of oral AST1306. In addition the effects of food on PK was tested.MethodsA modified Fibonacci 3 plus 3 dose-escalation design was employed to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) in patients with advanced solid tumors. The following dose levels were investigated: once daily (QD) at two dose levels (400-and 800 mg), twice daily (BID) in five dose levels (600-, 800-, 1000-, 1200- and 1500 mg), and three times daily (TID) in three dose levels (800-, 1000- and 1200 mg). In the PK and extension study, at least eight patients per dose cohort in three dose levels (maximum tolerated dose [MTD], one or two doses level lower than the MTD) were enrolled to evaluate the PK profiles.ResultsSeventy-one patients were enrolled, with breast (n?=?22) and lung cancers (n?=?14) being the most common primary cancers. The most frequent drug-related adverse events were grade 1 to 3 diarrhea and rash, grade 1 to 2 fatigue. During dose escalation, the key DLT was grade 3 diarrhea observed in 5 patients at 1000 mg BID (n?=?1), 1500 mg BID (n?=?1), 800 mg TID (n?=?1) and 1200 mg TID (n?=?2). AST1306 was rapidly absorbed and had moderate to high clearance. PK concentration parameters increased with dose over the range evaluated, with no evidence of accumulation over time. Under fed conditions, the mean T(max) was prolonged, C(max) was increased, and AUC(0-?) was raised. Of the 55 evaluable patients, 7 patients experienced partial responses, including 5 with breast cancer, 1 with lung cancer, and 1 with gastric cancer. The best response with stable disease for???6 months was achieved in 7 patients.ConclusionsBased on the DLT and PK profile, the RP2D was defined as 1000 mg TID with evidence of preliminary anti-tumor activity. Further studies are recommended.

Dataset Information

Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study.

Publications

Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets