Combining Chiauranib with Paclitaxel for Ovarian Cancer Treatment

A Multi-center, Double-blind, Randomized Phase III Clinical Trial of Chiauranib Plus Weekly Paclitaxel in Patients with Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer

This study is testing if adding a new drug called Chiauranib to the standard treatment of paclitaxel can help people with tough-to-treat ovarian cancer feel better.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 454 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Chipscreen Biosciences, Ltd. (Industry-sponsored)
• Drugs / interventions: Bevacizumab, Apatinib, Anlotinib, Fruquintinib, chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, China)
• Trial ID: NCT04921527 on ClinicalTrials.gov

What this trial studies

This phase 3 clinical trial evaluates the effectiveness and safety of Chiauranib in combination with weekly paclitaxel compared to a placebo with paclitaxel in patients suffering from platinum-refractory or platinum-resistant recurrent ovarian cancer. Chiauranib is a novel oral medication that targets multiple kinases involved in cancer progression and inflammation, aiming to improve treatment outcomes. Participants will be randomly assigned to receive either the combination treatment or the placebo, with paclitaxel administered every 21 days for up to six cycles, followed by continued treatment until disease progression for those showing a response.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 to 70 with confirmed platinum-refractory or platinum-resistant ovarian cancer.

Not a fit: Patients who have not received prior platinum-based chemotherapy or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat ovarian cancer.

How similar studies have performed: Other studies have shown promise with similar multi-targeted approaches in treating ovarian cancer, indicating potential for success.

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.

Where this trial is running

Shanghai, China

• Fudan University Shanghai Cancer Center — Shanghai, China, China (Recruiting)

Study contacts

• Principal investigator: Xiaohua Wu — Fudan university Shanghai cancer centre
• Study coordinator: Yu Chen

Conditions Ovarian Cancer; Relapsed or Refractory; Chiauranib; Paclitaxel