Ovarian Cancer, Relapsed or Refractory, Chiauranib, Paclitaxel
Conditions
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.
Interventions
DRUGchiauranib
50mg orally once daily
DRUGPlacebo
50mg orally once daily
DRUGPaclitaxel
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 ;
Sponsors
Chipscreen Biosciences, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival (PFS) | assessed up to 1 years | From the first time of treatment until the date of first documented progression or date of death from any cause, whichever comes first (Assessed by IRC) |
| overall survival (OS) | assessed up to 2 years | OS is defined as the length of time from treatment to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | assessed up to 2 years | DCR is defined as the Proportion of participants in partial, complete or stable desease according to RECIST 1.1. criteria |
| Quality of life (QoL) | assessed up to 2 years | QoL assessed by EORTC QLQ-OV28 |
| overall response rate (ORR) | assessed up to 2 years | ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| PK parameters of paclitaxel, chiauranib and M345 | assessed up to 2 years | PK parameters include but not limited to AUC, Cmax, Tmax etc. |
| Toxicity according to NCI CTCAE v5.0 criteria | assessed up to 2 years | tolerance of the treatment based on AE occurrence according to NCI CTCAE v5.0 criteria |
| duration of response (DOR) | assessed up to 2 years | From the first date of response until the date of first documented progression |
Countries
China
Contacts
Primary ContactYu Chen
Outcome results
None listed