CHIPRO: Chiauranib Plus Weekly Paclitaxel in Patients With Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: chiauranib
50mg orally once daily
Other Names:
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 ;
Other Names:
|
| Placebo Comparator: 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. |
Drug: Placebo
50mg orally once daily
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 ;
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- duration of response (DOR) [assessed up to 2 years]
From the first date of response until the date of first documented progression
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Willingness to sign a written informed consent document .
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Female, age ≥18 yrs and ≤70 yrs.
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Histological or cytological confirmation of epithelial ovarian cancer, carcinoma tube, or primary peritoneal carcinoma.
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Patients with platinum refractory or platinum resistant ovarian cancer:
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Platinum refractory: progression during the first platinum-based treatment or within 4 weeks after the first platinum-based primary therapy;
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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);
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Radiological progression during the last treatment administered;
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no more than 1 prior treatment regimens for recurrent disease.
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
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At least 1 lesion can be accurately measured, as defined by RECIST1.1.
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Laboratory criteria are as follows:
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Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets ≥90×109/L;
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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) ;
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Coagulation test: International Normalized Ratio (INR) < 1.5, activeated partial thromboplasting time (APTT) <1.5×ULN
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Life expectancy of at least 3 months.
Exclusion Criteria:
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Patients received vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor(VEGFR) inhibitor, like Apatinib, Anlotinib, Fruquintinib, Bevacizumab, etc., or Aurora kinase inhibitors.
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Patients received weekly paclitaxel therapy.
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Has known allegies to Chiauranib, paclitaxel or any of the excipients.
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Biological therapy, immunotherapy, hormonal therapy within 28 days prior to the first dose of study drug.
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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.
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Treatment with an investigational agent/instrument within 28 days prior to first dose of study drug.
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Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1.
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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.
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History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
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clinically significant central/peripheral nervous system disease.
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Have uncontrolled or significant cardiovascular disease, including:
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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.
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primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al)
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History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms prior to study entry
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Symptomatic coronary heart disease requiring treatment with agents
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History of hypertension treated by≥2 agents, or the Blood pressure (Bp) ≥140/90 mmHg prior to study entry.
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Other condition investigator considered inappropriate
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Significant intravenous or arterial thrombosis, such as cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
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History of active bleeding within the past 2 months, patients with bleeding potential during the screening period, or receiving anticoagulation therapy.
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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.
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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.
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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.
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Screening for HIV antibody positive.
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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.
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Active infection requiring oral or intravenous systemic antimicrobial therapy during the screening period.
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Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study.
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History of organ transplantation or allo-HSCT.
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Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study.
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Candidates with drug and alcohol abuse.
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Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study.Pregnant or breastfeeding women.
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Any other condition which is inappropriate for the study in the opinion of the investigators.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fudan University Shanghai Cancer Center | Shanghai | China | 200032 |
Sponsors and Collaborators
- Chipscreen Biosciences, Ltd.
Investigators
- Principal Investigator: Xiaohua Wu, Fudan university Shanghai cancer centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAR301