Phase Ib Study of Chiauranib in Patients With Ovarian Cancer

Phase 1

Completed

• Conditions: Ovarian Cancer
• Interventions: Drug: Chiauranib

• Registration Number: NCT03166891
• Lead Sponsor: Chipscreen Biosciences, Ltd.

Brief Summary

Chiauranib may stop the growth of tumor cells by blocking Aurora kinase B（Aurora B）、VEGFR/PDGFR/c-Kit、CSF-1R targets. This clinical trial is studying the efficacy and safety of chiauranib(50mg，QD，PO) works in treating patients with relapsed or refractory ovarian cancer, in the meantime, exploring the latent biomarkers accompany with chiauranib, as well as the relevancy of which and clinical benefit.

Detailed Description

The purpose of this study is to assess the efficacy and safety include adverse events, vital signs, laboratory tests ,etc., of Chiauranib in ovarian cancer patients due to the outcomes of the phase I study, and to explore the relevance between the latent biomarkers of Chiauranib and clinical benefit.

Study Timeline

• Study First Submitted: 2017-05-22
• Study First Submitted QC: 2017-05-23
• Study First Posted: 2017-05-25
• Study Start: 2017-12-15
• Primary Completion: 2019-03-20
• Study Completion: 2019-03-20
• Status Verified: 2019-07
• Last Update Submitted: 2020-01-14
• Last Update Posted: 2020-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 25

Inclusion Criteria

1. Female, aged ≥ 18 yrs and ≤70 yrs;

2. Histological or cytological confirmation of epithelial ovarian cancer, carcinoma tubae, or primary peritoneal carcinoma.

3. Patients have received platinum containing chemotherapy, a) platinum resistant disease (disease progression within 6 months of the last receipt of platinum-based chemotherapy), the disease has progressed or relapsed after at least 2 different chemotherapy regimens; b) platinum sensitive disease (disease progression after 6 months of the last receipt of platinum-based chemotherapy), the disease has progressed or relapsed at least 2 different chemotherapy regimens, or the patients refuse any chemotherapy.

4. At least 1 lesion can be accurately measured, as defined by RECIST1.1.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

6. Subjects received anti-cancer therapy (including chemotherapy, radiotherapy, immunotherapy and surgical therapy, et al) should beyond 4 weeks prior to study entry; Subjects received mitomycin chemotherapy should beyond 6 weeks prior to study entry.

7. Laboratory criteria are as follows:

   Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets >=90×109/L Biochemistry test: total bilirubin≦1.5×ULN; alanine aminotransferase(ALT) ,aspartate aminotransferase(AST)≦1.5×ULN; (ALT,AST≦5×ULN if liver involved) ;serum creatinine(cr)≦1.5×ULN; Coagulation test: International Normalized Ratio (INR) < 1.5.

8. Life expectancy of at least 12 weeks.

9. Willingness to sign a written informed consent document.

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Exclusion Criteria

1. Patients with prior invasive malignancies with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, unless received curative treatment and with documented evidence of no recurrence in the past five years;

2. Clinical evidence of central nervous system involvement;

3. Have uncontrolled or significant cardiovascular disease, including:

   1. Congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) < 50% requiring treatment with agents during screening stage.
   2. primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al)
   3. History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms prior to study entry
   4. Symptomatic coronary heart disease requiring treatment with agents
   5. Uncontrolled hypertension (> 140/90 mmHg) by single agent.

4. Have active bleeding current thrombotic disease, patients with bleeding potential ,or receiving anticoagulation therapy; within 2 months prior to screening;

5. Proteinuria positive(≥1g/24h).

6. History of deep vein thrombosis or pulmonary embolism;

7. Have unsolved toxicities (> grade 1) from prior anti-cancer therapy;

8. 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.

9. History of organ transplantation.

10. Major surgery within 6 weeks and minor surgery within 2 weeks prior to screening (excluding placement of vascular access or biopsy) that involved general anaesthesia or respiratory assistance.

11. Serologically positive for HIV, hepatitis B or C, or other serious infectious diseases.

12. History of interstitial lung disease(ILD).

13. Previous treatment with aurora kinase inhibitors.

14. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;

15. Candidate with drug and alcohol abuse.

16. Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study (both male and female participants).Pregnant or breastfeeding women. Female participants must have a negative urinary or serum pregnancy test when done or have evidence of post-menopausal status (Defined as absence of menstruation for greater than 12 months, bilateral oophorectomy or hysterectomy).

17. 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 Chiauranib capsules 50mg, orally once daily, 28 days as a cycle.

Primary Outcome Measures

Name	Time	Method
Overall response rate(ORR)	assessed up to 2 years	ORR will be calculated from the data obtained from the end visit

Secondary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events	measured through 2 years	measured by adverse events (AE), serious adverse events (SAE), abnormal vital signs，electrocardiograph(ECG) and abnormal laboratory results according to CTCAE V4.03
Progression-free survival (PFS)	assessed up to 2 years	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first
Time to progression(TTP)	through treatment completion, up to 2 years	duration from date of treatment until the date of first documented progression
Duration of response (DOR)	assessed up to 2 years	From the first date of response until the date of first documented progression
Overall survival(OS)	assessed up to 2 years	Time from treatment to death from any cause
16 week-disease control rate(16W-DCR)	assessed up to 2 years	Rate of the patients with disease control longer than 6 weeks

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China