Phase Ib Study of Chiauranib in Patients With Ovarian Cancer

Efficacy and Safety of Chiauranib in Relapsed/Refractory Ovarian Cancer: a Single-arm, Open-label, Multi-site, Exploratory Study

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Chiauranib

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 Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chiauranib; Patients take Chiauranib capsules 50mg, orally once daily, 28 days as a cycle.	Drug: Chiauranib; Take 50mg orally once daily; Other Names: CS2164

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate(ORR)	ORR will be calculated from the data obtained from the end visit	assessed up to 2 years

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunohistochemical(IHC) staining results of Aurora B、CSF-1R and Myc protein	The IHC staining results were assigned a mean follows: 0, negative; 1, weak; 2, moderate; and 3, strong. The frequency of positive cells was defined as follows: 0, less than 5%; 1, 5% to 25%; 2, 26% to 50%; 3, 51% to 75%; and 4,greater than 75%.	assessed up to 2 years
Any single mutation of oncogene and copy number variation in ctDNA(single gene analysis)		assessed up to 2 years
Mutation of polygene and copy number variation in signal pathway(multi-gene analysis)		assessed up to 2 years

Collaborators and Investigators

• Sponsor: Chipscreen Biosciences, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): March 20, 2019
• Study Completion (Actual): March 20, 2019

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (Actual): May 25, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: ovarian cancer, relapsed or refractory,chiauranib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Chiauranib
• Other Study ID Numbers: CAR102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No