Indication: Patients with advanced recurrent or metastatic thymic carcinoma. Phase IIa (China only):Approximately 6 patients. Phase IIb (China only):Approximately 54 patients.
This study consists of two parts: a Phase IIa study and a Phase IIb study. Phase IIa study: A single-arm, open-label study to evaluate the safety and tolerability of Lucitanib administered at 15 mg once daily for three consecutive weeks followed by one week off treatment in patients with advanced solid tumors who have failed standard therapy, have no effective treatment options, or are unwilling to receive standard therapy. Phase IIb study: A randomized, double-blind, placebo-controlled, multicenter study to evaluate Lucitanib in patients with advanced, recurrent, or metastatic thymic carcinoma who have failed at least first-line chemotherapy and are not eligible for surgical resection or definitive radiotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
74
Phase IIa: The investigational product will be orally administrated when fasting at dose level of lucitanib 15 mg, QD, 3 weeks on and 1 week off
Phase IIb: The investigational product will be orally administrated when fasting at dose level of lucitanib 10 mg QD
Phase IIb: The investigational product will be orally administrated when fasting at dose level of Placebo QD
Beijing Cancer Hospital
Beijing, China
Peking University People's Hospital
Beijing, China
Xuanwu Hospital Capital Medicine University
Beijing, China
Phase IIa:Safety and Tolerability
The safety and tolerability of lucitanib will be evaluated based on the incidence, type, severity, and outcome of adverse events (AEs) and treatment-emergent adverse events (TEAEs), including dose-limiting toxicities (DLTs) and other adverse events occurring during the treatment period. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.
Time frame: From first dose through 28 days after the last dose
Phase IIb:Progression-free survival (PFS) by independent review committee
Progression-free survival is defined as the time from the date of randomization to the date of disease progression or death from any cause, whichever occurs first, as assessed by independent review committee according to RECIST Version 1.1.
Time frame: Up to approximately 24 months
Phase IIa: Progression-free survival (PFS) by investigator
Progression-free survival is defined as the time from the date of first dose of lucitanib to the date of disease progression or death from any cause, whichever occurs first, as assessed by the investigator according to RECIST Version 1.1
Time frame: Up to approximately 24 months
Phase IIa: Objective response rate (ORR)
Objective response rate is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR), as assessed by the investigator according to RECIST Version 1.1.
Time frame: Up to approximately 24 months
Phase IIa: Disease Control Rate (DCR)
Disease control rate is defined as the proportion of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed by the investigator according to RECIST Version 1.1.
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Hunan Cancer Hospital
Changsha, China
Fujian Medicine University Union Hospital
Fuzhou, China
Sun Yat-sen University Cancer Center
Guangzhou, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, China
Zhejiang Cancer Hospital
Hangzhou, China
Fudan University Shanghai Cancer Center
Shanghai, China
Shanghai Chest Hospital
Shanghai, China
...and 6 more locations
Time frame: Up to approximately 24 months
Phase IIb: Progression-free survival (PFS) by investigator assessment
Progression-free survival is defined as the time from the date of randomization to the date of disease progression or death from any cause, whichever occurs first, as assessed by the investigator according to RECIST Version 1.1.
Time frame: Up to approximately 24 months
Phase IIb: 6-month progression-free survival rate
The 6-month progression-free survival rate is defined as the proportion of participants who remain alive and free of disease progression at 6 months after randomization, as assessed according to RECIST Version 1.1.
Time frame: 6 months after randomization
Phase IIb: Objective response rate (ORR)
Objective response rate is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR), according to RECIST Version 1.1.
Time frame: Up to approximately 24 months
Phase IIb: Disease control rate (DCR)
Disease control rate is defined as the proportion of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD), according to RECIST Version 1.1.
Time frame: Up to approximately 24 months
Phase IIb: Duration of response (DoR)
Duration of response is defined as the time from the date of first documented complete response or partial response to the date of disease progression or death from any cause, whichever occurs first, as assessed according to RECIST Version 1.1.
Time frame: From the date of first documented response until disease progression or death, assessed up to approximately 24 months
Phase IIb: Overall survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death from any cause.
Time frame: From the date of randomization until death from any cause, assessed up to approximately 48 months
Phase IIb: Safety and tolerability
The safety and tolerability of lucitanib will be evaluated based on the incidence, type, severity, and outcome of adverse events (AEs) and treatment-emergent adverse events (TEAEs) occurring during the treatment period and safety follow-up. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.
Time frame: From first dose through 28 days after the last dose
Phase IIa:Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUClast)
AUClast of lucitanib in plasma will be evaluated based on plasma concentrations of lucitanib collected pre-dose and at 30 min, 1, 2, 3, 4, 8, and 12 hours post-dose.
Time frame: Day 1 and Day 15
Phase IIa:Area Under the Concentration-Time Curve over 24 Hours (AUC24)
AUC24 of lucitanib in plasma will be evaluated based on plasma concentrations of lucitanib collected pre-dose and at 30 min, 1, 2, 3, 4, 8, and 12 hours post-dose.
Time frame: Day 1 and Day 15
Phase IIa:Maximum Observed Concentration (Cmax)
Maximum observed plasma concentration (Cmax) of lucitanib will be evaluated based on plasma concentrations collected pre-dose and at 30 min, 1, 2, 3, 4, 8, and 12 hours post-dose.
Time frame: Day 1 and Day 15
Phase IIa:Minimum Observed Concentration (Cmin)
Minimum observed plasma concentration (Cmin) of lucitanib will be evaluated based on plasma concentrations collected pre-dose and at 30 min, 1, 2, 3, 4, 8, and 12 hours post-dose.
Time frame: Day 1 and Day 15
Phase IIa:Accumulation Ratio (Racc)
Accumulation ratio (Racc) of lucitanib will be evaluated based on plasma concentrations on Day 1 and Day 15.
Time frame: Day 15
Phase IIa:Terminal Half-Life (t1/2)
Terminal half-life (t1/2) of lucitanib will be evaluated based on plasma concentrations collected following dosing.
Time frame: Day 1 and Day 15
Phase IIa:Clearance (CL)
Clearance (CL) of lucitanib will be evaluated based on plasma concentrations collected following dosing.
Time frame: Day 1 and Day 15