This is a Phase 1b/2, single-arm, open-label, dose-escalation study including 2 stages: Phase 1b: Dose-Escalation Stage (Single-Dose and Consecutive-Dose Periods) Phase 2: recommended Phase 2 dose (RP2D) of chiauranib will be given to all patients enrolled in this phase once daily for 28-day cycles continuously with no interruption between cycles.
Phase 1b: Patients with advanced solid malignant tumor (including SCLC, NSCLC, colorectal carcinoma, pancreatic carcinoma, hepatocellular carcinoma, ovarian cancer, neuroendocrine tumors, non-Hodgkin's lymphoma and others) that has relapsed from or is refractory to standard therapy or for which no standard therapy exists will be enrolled to the 35 mg, 50 mg and 65 mg dose cohorts in this stage. The starting dose is 35 mg, and each higher dose cohort will not enroll until the lower dose is deemed safe. After screening, eligible patients will be enrolled sequentially in 3 dose-escalating cohorts. Based on an estimated average body weight of 60 kg, the initial dose of chiauranib will be 35 mg once daily, and the dose will be escalated to 50 mg and 65 mg once daily, depending on the occurrence and frequency of DLTs. The 3+3 design will be employed in dose escalation decisions. Each dose cohort will enroll at least 3 patients. Overenrolling dosing cohorts is allowed to allow for potential screen failures and/or subjects who end up being not evaluable by not completing the DLT evaluation period. Each subject will undergo both a single-dose period (6 days) and a consecutive-dose (1 cycle of 28 days) period, as described below. DLTs will be evaluated during this period (a total of 34 days). Phase 2: SCLC patients with progressive disease or recurrence after at least 2 previous regimens, including one platinum-based chemotherapy, will be enrolled in this stage. The RP2D will be given to all subjects enrolled in this stage. Subjects will take the RP2D chiauranib once daily for 28-day cycles continuously with no interruption between cycles.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Phase 1b: Each patient will undergo both a single-dose period (6 days) and a consecutive-dose (1 cycle of 28 days) period Phase 2: Patients will take the RP2D once daily for 28-day cycles continuously with no interruption between cycles
California Cancer Associates-Encintas
Encinitas, California, United States
RECRUITINGProvidence/St. Joe Cancer Institute/Crosson Cancer Institute
Fullerton, California, United States
RECRUITINGIncidence of adverse events (AEs) and other safety parameters
Number of patients experienced AEs
Time frame: Until 30 days after a patient takes the last dose of the study drug
Incidence and characteristics of DLTs
Number of patients experienced any dose limited toxicity
Time frame: 34 days
MTD and recommended Phase 2 dose (RP2D)
Determination of recommended phase II dose
Time frame: 34 days
Time to maximum concentration (Tmax)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Maximum plasma concentration (Cmax)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Area under the plasma concentration-time curve from 0 to infinity (AUC 0-inf)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Half-life (t½)
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Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
RECRUITINGDana Farber Cancer Institue
Boston, Massachusetts, United States
RECRUITINGKarmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGComprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
RECRUITINGGabrail Cancer Center Research
Canton, Ohio, United States
RECRUITINGOU Health
Oklahoma City, Oklahoma, United States
RECRUITINGSarah Cannon Research Center
Nashville, Tennessee, United States
RECRUITINGNorth Houston Cancer Clinics
Huntsville, Texas, United States
RECRUITING...and 1 more locations
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Trough plasma concentration (Cmin)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Area under the plasma concentration-time curve (AUC0-t)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Oral clearance (CL/F)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
accumulation ratio
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Steady state plasma concentration (Css)
PK Profile
Time frame: Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)
Objective response rate (ORR)
preliminary efficacy of chiauranib
Time frame: 6 months
disease control rate (DCR)
preliminary efficacy of chiauranib
Time frame: 6 months
duration of response (DoR)
preliminary efficacy of chiauranib
Time frame: 6 months
progression-free survival (PFS)
preliminary efficacy of chiauranib
Time frame: 6 months
overall survival (OS)
preliminary efficacy of chiauranib
Time frame: 6 months
Correlation between ATRX gene mutation and efficacy
Efficacy outcomes in patients with ATRX gene mutation and wild-type respectively.
Time frame: 6 months