Phase I Study of Chiauranib in Patients With Advanced Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chiauranib Patients take a single dose of Chiauranib capsules for the pharmacokinetic study,then off for 5 days before the first cycle begins. In the subsequent treatment cycles, Chiauranib capsules are given orally once daily, 28 days as a cycle. |
Drug: Chiauranib
Take orally
Other Names:
|
Outcome Measures
Primary Outcome Measures
- dose-limiting toxicity (DLT) [day 1-28]
- Number of Adverse Events [An expected average of 8 months]
Secondary Outcome Measures
- pharmacokinetic profile of Chiauranib [On day 1,8,15,22,25,26,27,28]
- Evidence of benefit [An expected average of 8 months]
clinical benefit rate (complete response (CR),partial response (PR),stable disease (SD) > 8 weeks),duration of response (DOR),time to progression (TTP), or tumor marker improvement, if appropriate
- Pharmacodynamic profile of Chiauranib [On day 15,28]
Plasma biomarkers: soluble vascular endothelial growth factor receptors (sVEGFR2), vascular endothelial growth factor (VEGF) Tumor tissue biomarkers: Aurora B, phospho-histone H3
Eligibility Criteria
Criteria
Inclusion Criteria:
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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;
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Patients with advanced solid tumors refractory to standard therapy or for which no standard therapy exists;
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Body mass index (BMI) is between 18 and 28;
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Age: 18~65 years;
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
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Laboratory criteria are as follows:
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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
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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
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Coagulation test: International Normalized Ratio (INR) < 1.5
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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;
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Willingness to sign a written informed consent document
Exclusion Criteria:
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Life expectation < 3 months;
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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;
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Have uncontrolled or significant cardiovascular disease, including:
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Myocardial infarction (< the last 12 months)
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Uncontrolled angina (< the last 6 months)
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Congestive heart failure (< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) < 50% prior to study entry
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History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP)
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History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 450 ms prior to study entry
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History of cerebrovascular accident
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Symptomatic coronary heart disease requiring treatment with agents
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Uncontrolled hypertension (> 140/90 mmHg) by single agent;
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Have active bleeding , current thrombotic disease, or patients with bleeding potential receiving anticoagulation therapy;
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History of deep vein thrombosis or pulmonary embolism;
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Have unsolved toxicities (> grade 1) from prior anti-cancer therapy;
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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;
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Have symptomatic brain metastasis;
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History of organ transplantation;
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Proteinuria positive;
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Congenital or acquired immunodeficiency, active infections;
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Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;
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Any other condition which is inappropriate for the study in the opinion of the investigators.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer Hospital, Chinese Academy of Medical Sciences | Beijing | Beijing | China | 100021 |
Sponsors and Collaborators
- Chipscreen Biosciences, Ltd.
Investigators
- Principal Investigator: Yuankai Shi, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAR101