Chiauranib Plus Weekly Paclitaxel in Patients with Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer

NCT ID: NCT04921527

Last Updated: 2024-10-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 454 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-20
• Study Completion Date: 2025-07-31

Brief Summary

This randomized, double-blind, 2-arm study will evaluate the efficacy and safety of Chiauranib plus weekly paclitaxel versus placebo plus weekly paclitaxel in patients with Platinum-refractory or Platinum-resistant Recurrent ovarian cancer.

Detailed Description

Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRa and c-Kit), mitosis-related kinase Aurora B and chronic inflammationrelated kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. In particular, Chiauranib showed very high selectivity in the kinase inhibition profile with little activity on off-target non-receptor kinases, proteins, GPCR and ion channels, indicative of a better drug safety profile in terms of clinical relevance.

Patients will be randomized to receive treatment with either paclitaxel + Chiauranib or paclitaxel + placebo. Paclitaxel will be repeated every 21 days for a maximum of 6 cycles. Patients with objective response/stable disease after completing 6 courses of chemotherapy will continue Chiauranib or placebo until progression.

Conditions

Ovarian Cancer; Relapsed or Refractory; Chiauranib; Paclitaxel

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Chiauranib plus weekly paclitaxel

Patients receive the combined treatment of chiauranib plus paclitaxel, 21 days for a cycle, 6 cycles at most,Chiauranib is given orally, 50mg once daily. Paclitaxel is given in intravenous infusion on Day 1, 8 and 15. After 6 cycles combined treatment, patients enter the single agent therapy of chiauranib.

Group Type: EXPERIMENTAL

chiauranib

Intervention Type: DRUG

50mg orally once daily

Paclitaxel

Intervention Type: DRUG

at the first cycle, 60mg/m2, i.v infusion on day 1, 8 and 15 ; at the begining of the second cycle, after a comprehensive assessment , investigators decide whether to increase the dosage to 80mg/m2, i.v infusion on day 1, 8 and 15 ;

placebo plus weekly paclitaxel

Patients receive the combined treatment of placebo plus paclitaxel, 21 days for a cycle, 6 cycles at most,placebo is given orally, 50mg once daily. Paclitaxel is given in intravenous infusion on Day 1, 8 and 15. After 6 cycles combined treatment, patients enter the single agent therapy of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

50mg orally once daily

Paclitaxel

Intervention Type: DRUG

at the first cycle, 60mg/m2, i.v infusion on day 1, 8 and 15 ; at the begining of the second cycle, after a comprehensive assessment , investigators decide whether to increase the dosage to 80mg/m2, i.v infusion on day 1, 8 and 15 ;

Interventions

chiauranib

50mg orally once daily

Intervention Type: DRUG

Placebo

50mg orally once daily

Intervention Type: DRUG

Paclitaxel

at the first cycle, 60mg/m2, i.v infusion on day 1, 8 and 15 ; at the begining of the second cycle, after a comprehensive assessment , investigators decide whether to increase the dosage to 80mg/m2, i.v infusion on day 1, 8 and 15 ;

Intervention Type: DRUG

Other Intervention Names

CS2164; Anzatax

Eligibility Criteria

Inclusion Criteria

• Willingness to sign a written informed consent document .
• Female, age ≥18 yrs and ≤70 yrs.
• Histological or cytological confirmation of epithelial ovarian cancer, carcinoma tube, or primary peritoneal carcinoma.
• Patients with platinum refractory or platinum resistant ovarian cancer:

• Platinum refractory: progression during the first platinum-based treatment or within 4 weeks after the first platinum-based primary therapy;
• Platinum resistant: progression during the platinum-based treatment except for platinum refractory, or within 6 months after the last receipt of platinum-based treatment (patients have received platinum containing chemotherapy at least 4 weeks);
• Radiological progression during the last treatment administered;
• no more than 1 prior treatment regimens for recurrent disease.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• At least 1 lesion can be accurately measured, as defined by RECIST1.1.
• 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: serum creatinine(cr) <1.5×ULN; total bilirubin<1.5×ULN; alanine aminotransferase(ALT) ,aspartate aminotransferase(AST)≤2.5×ULN; (ALT,AST≦5×ULN if liver involved) ;
• Coagulation test: International Normalized Ratio (INR) < 1.5, activeated partial thromboplasting time (APTT) <1.5×ULN
• Life expectancy of at least 3 months.

Exclusion Criteria

• Patients received vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor(VEGFR) inhibitor, like Apatinib, Anlotinib, Fruquintinib, Bevacizumab, etc., or Aurora kinase inhibitors.
• Patients received weekly paclitaxel therapy.
• Has known allegies to Chiauranib, paclitaxel or any of the excipients.
• Biological therapy, immunotherapy, hormonal therapy within 28 days prior to the first dose of study drug.
• prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
• Treatment with an investigational agent/instrument within 28 days prior to first dose of study drug.
• Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1.
• Patients with prior invasive malignancies in the past five years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
• clinically significant central/peripheral nervous system disease.
• Have uncontrolled or significant cardiovascular disease, including:

• 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.
• primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al)
• History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms prior to study entry
• Symptomatic coronary heart disease requiring treatment with agents
• History of hypertension treated by≥2 agents, or the Blood pressure (Bp) ≥140/90 mmHg prior to study entry.
• Other condition investigator considered inappropriate
• Significant intravenous or arterial thrombosis, such as cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• History of active bleeding within the past 2 months, patients with bleeding potential during the screening period, or receiving anticoagulation therapy.
• CT or MRI of the chest during the screening period shows interstitial lung disease or pulmonary fibrosis or lung inflammation that requires treatment, or within 6 months before the first dose, history of pneumonia requiring oral or intravenous steroid treatment, history of immune-associated pneumonia after treatment of PD1/PDL1 inhibitor.
• Have clinical significant gastrointestinal abnormality that would impair the ingestion, transportation or absorption of oral agents, history of gastrointestinal perforation or abdominal fistula, peptic ulcer disease within 6 months prior to first dose of study drug or GI obstruction within the past 3 months.
• Pleural fluid, ascites or pericardial effusion with significant symptoms or required treatment of puncture or drainage during the screening period, or history of drainage for therapy within 1 months prior to first dose of study drug.
• Screening for HIV antibody positive.
• Screening test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with virus replication, hepatitis C antibody (HCV-Ab) positive with virus replication.
• Active infection requiring oral or intravenous systemic antimicrobial therapy during the screening period.
• Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study.
• History of organ transplantation or allo-HSCT.
• Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study.
• Candidates with drug and alcohol abuse.
• Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study.Pregnant or breastfeeding women.
• Any other condition which is inappropriate for the study in the opinion of the investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chipscreen Biosciences, Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiaohua Wu

Role: PRINCIPAL_INVESTIGATOR

Fudan university Shanghai cancer centre

Locations

Fudan University Shanghai Cancer Center

Shanghai, China, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yu Chen

Role: CONTACT

chenyu@chipscreen.com

8610-56102349

Facility Contacts

Xiaohua Wu, MD

Role: primary

13601772486

Xiaohua Wu, MD

Role: backup

Other Identifiers

CAR301

Identifier Type: -

Identifier Source: org_study_id