Clinical trial NCT02122809: Phase I Study of Chiauranib in Patients With Advanced Solid Tumors
Official title: Phase I Safety and Pharmacokinetics Study of Chiauranib in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Chiauranib, advanced solid tumors, phase 1 study
Lead sponsor: Chipscreen Biosciences, Ltd.
Sponsor class: INDUSTRY
First posted: 2014-04-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chiauranib administered orally over a range of doses in patients with advanced solid tumors.

Detailed description: The purpose of this study is to assess the tolerability and safety include adverse events, vital signs, laboratory tests ,etc., of a range of doses of Chiauranib in solid tumor patients, and to determine the dose limit toxicity and the maximum tolerable dose.

Eligibility criteria: Inclusion Criteria:

1. Histological or cytological confirmation of advanced solid tumor, including non-small cell lung cancer, colorectal cancer, ovarian cancer, renal cell carcinoma, gastrointestinal stromal tumor, gastric cancer, et al;
2. Patients with advanced solid tumors refractory to standard therapy or for which no standard therapy exists;
3. Body mass index (BMI) is between 18 and 28;
4. Age: 18\~65 years;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
6. Laboratory criteria are as follows:

   1. Complete blood count: hemoglobin (Hb) ≥100g/L (no blood transfusion within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L ; platelets \>=100×109/L
   2. Biochemistry test: serum creatinine \<=1.5×upper limit of normal (ULN); total bilirubin≦1.5×ULN; alanine aminotransferase / aspartate aminotransferase≦1.5×ULN; fasting triglyceride (TG) \<= 3.0 mmol/L; total cholesterol \<= 7.75 mmol/L
   3. Coagulation test: International Normalized Ratio (INR) \< 1.5
7. Women of child-bearing potential should be non-lactating patients, and must agree to use effective contraceptive methods prior to study entry, during study participation, and up to 6 months following completion of therapy. A serum or urine pregnancy test within 7 days before enrollment must be negative; Men must agree to use effective contraceptive methods during study participation and up to 6 months following completion of therapy;
8. Willingness to sign a written informed consent document

Exclusion Criteria:

1. Life expectation \< 3 months;
2. Subjects received anti-cancer therapy (including chemotherapy, radiotherapy, targeted therapy and endocrine therapy, et al) within 4 weeks prior to study entry; Subjects received nitrosoureas or mitomycin chemotherapy within 6 weeks prior to study entry;
3. Have uncontrolled or significant cardiovascular disease, including:

   1. Myocardial infarction (\< the last 12 months)
   2. Uncontrolled angina (\< the last 6 months)
   3. Congestive heart failure (\< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) \< 50% prior to study entry
   4. History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP)
   5. History of significant QT interval prolongation, or Corrected QT Interval (QTc) \> 450 ms prior to study entry
   6. History of cerebrovascular accident
   7. Symptomatic coronary heart disease requiring treatment with agents
   8. Uncontrolled hypertension (\> 140/90 mmHg) by single agent;
4. Have active bleeding , current thrombotic disease, or patients with bleeding potential receiving anticoagulation therapy;
5. History of deep vein thrombosis or pulmonary embolism;
6. Have unsolved toxicities (\> grade 1) from prior anti-cancer therapy;
7. Have clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, that would impair the ingestion,transportation or absorption of oral agents, or patients undergone gastrectomy;
8. Have symptomatic brain metastasis;
9. History of organ transplantation;
10. Proteinuria positive;
11. Congenital or acquired immunodeficiency, active infections;
12. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;
13. Any other condition which is inappropriate for the study in the opinion of the investigators.

Primary outcomes:
measure: dose-limiting toxicity (DLT)
timeFrame: day 1-28
measure: Number of Adverse Events
timeFrame: An expected average of 8 months
Secondary outcomes:
measure: pharmacokinetic profile of Chiauranib
timeFrame: On day 1,8,15,22,25,26,27,28
measure: Evidence of benefit
timeFrame: An expected average of 8 months
measure: Pharmacodynamic profile of Chiauranib
timeFrame: On day 15,28
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sun Y, Yang L, Hao X, Liu Y, Zhang J, Ning Z, Shi Y. Phase I dose-escalation study of chiauranib, a novel angiogenic, mitotic, and chronic inflammation inhibitor, in patients with advanced solid tumors. J Hematol Oncol. 2019 Jan 14;12(1):9. doi: 10.1186/s13045-018-0695-0.