Phase I Study of Chiauranib in Patients With Advanced Solid Tumors

Solid Tumors Clinical Trial

Official title:

Phase I Safety and Pharmacokinetics Study of Chiauranib in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02122809
• Other study ID #: CAR101
• Status: Completed
• Phase: Phase 1
• First received: April 22, 2014
• Last updated: June 16, 2016
• Start date: February 2014
• Est. completion date: June 2016

Study information

• Verified date: June 2016
• Source: Chipscreen Biosciences, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Chiauranib
Take orally

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chipscreen Biosciences, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	dose-limiting toxicity (DLT)		day 1-28	Yes
Primary	Number of Adverse Events		An expected average of 8 months	Yes
Secondary	pharmacokinetic profile of Chiauranib		On day 1,8,15,22,25,26,27,28	No
Secondary	Evidence of benefit	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	An expected average of 8 months	No
Secondary	Pharmacodynamic profile of Chiauranib	Plasma biomarkers: soluble vascular endothelial growth factor receptors (sVEGFR2), vascular endothelial growth factor (VEGF) Tumor tissue biomarkers: Aurora B, phospho-histone H3	On day 15,28	No