Phase I Study of Chiauranib in Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Solid Tumors
• Interventions: Drug: Chiauranib

• Registration Number: NCT02122809
• Lead Sponsor: Chipscreen Biosciences, Ltd.

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.

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-04-22
• Study First Submitted QC: 2014-04-23
• Study First Posted: 2014-04-25
• Primary Completion: 2016-04
• Status Verified: 2016-06
• Study Completion: 2016-06
• Last Update Submitted: 2016-06-16
• Last Update Posted: 2016-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chiauranib	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.

Primary Outcome Measures

Name	Time	Method
dose-limiting toxicity (DLT)	day 1-28
Number of Adverse Events	An expected average of 8 months

Secondary Outcome Measures

Name	Time	Method
pharmacokinetic profile of Chiauranib	On day 1,8,15,22,25,26,27,28
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
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

Trial Locations

Locations (1)

Cancer Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China