A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 3 Clinical Study of Chiauranib Capsule in Patients With Progressed or Relapsed Small-cell Lung Cancer After 2 Lines Chemotherapy (CHIS)
A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 3 Clinical Study of Chiauranib Capsule in Patients With Progressed or Relapsed Small-cell Lung Cancer After 2 Lines Chemotherapy (CHIS)
Chiauranib , which simultaneously targets against VEGFR/Aurora B/CSF-1R, several key kinases involved in tumor angiogenesis, tumor cell mitosis, and chronic inflammatory microenvironment.
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.
In July 2017, the sponsor initiated a phase Ib/II trial (CAR105). As of October 9, 2020, a total of 42 subjects entered the safety analysis and 41 subjects entered the efficacy analysis. The results of the phased trial analysis show the preliminary efficacy of this product in the treatment of SCLC at ≥3 lines.
This clinical trial is studying the efficacy and safety of chiauranib works in treating patients with relapsed or refractory small cell lung cancer, in the meantime, exploreing the latent biomarkers accompany with chiauranib, as well as the relevancy of which and clinical benefit.
Inclusion Criteria:
Male or female, age ≥ 18 years and ≤75 years;
Cytologically or histologically confirmed small cell lung cancer;
Patients have received at least 2 different systemic chemotherapy regimens (contained platinum based regimen) , and progressed or relapsed
At least one measurable lesion that can be accurately assessed ( RECIST1.1 criteria). If the only site of measurable disease is in a previously irradiated area, the patient must have documented progression of disease in this area.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Laboratory criteria are as follows:
Life expectancy of at least 3 months.
All patients must have given signed, informed consent prior to registration on study.
Exclusion Criteria:
Patients who known to brain metastases with neurological symptoms;
Screening period imaging shows that the tumor has invaded the periphery of important blood vessels or the investigator judges that the tumor is likely to invade important blood vessels and cause hemorrhage during the trial
Pleural fluid, ascites, pericardial effusion with clinical symptoms or need to be drained during the screening period
Patients with second primary cancer, except: adequately treated basal cell or squamous cell skin cancer, curatively treated in-situ cancer of the cervix, unless received curative treatment and with documented evidence of no recurrence during the past five years
Patients who have been used aurora kinase inhibitors, or VEGF/VEGFR inhibitors
Patients have used any anti-cancer therapy, including adiotherapy, chemotherapy, immunotherapy, target therapy, and other anti-tumor treatments within 28 days before the first dose
Patients have used experimental drugs or devices within 28 days before the first dose
Patients received major surgical operations within 28 days before the first dose, or patients with serious non-healing wounds, ulcer or fracture at the time of screening
With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy
Patients with uncontrolled or significant cardiovascular disease, including:
Obstructive atelectasis that requires chest radiotherapy or surgery during the screening period or 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
Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction, After small bowel resection,etc), or undergone gastrectomy, or history of gastrointestinal perforation
Proteinuria positive(≥1g/24h)
Active bleeding within 2 months before the first dose, or anticoagulant drugs are being taken during the screening period, or the investigator judges that there is a high risk of bleeding during the screening period
History of deep vein thrombosis or pulmonary embolism within 6 months before the first dose
Active infections that require systemic treatment (oral, intravenous infusion) during the screening period
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
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
Women of childbearing potential not willing to use and utilize an adequate method of contraception (such as intrauterine device, contraceptive and condom) throughout treatment and for at least 12 weeks after the last dose; pregnant or breastfeeding women; the result of urine pregnancy test was positive at screening; Man participants not willing to use and utilize an adequate method of contraception throughout treatment.
Any other condition which is inappropriate for the study according to investigators' judgment.