This is a phase I, multi-center clinical trial to evaluate the safety, tolerability, antitumor activities and pharmacokinetics of IN10018 as monotherapy or in combination with docetaxel in previously-treated locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Eligibility patients will be enrolled into the study and assigned to treatment groups: 1) IN10018 monotherapy group, and 2) IN10018+Docetaxel combination group. This study contains 2 parts of dose escalation and dose expansion for each treatment group. The monotherapy group will enroll patients failed to respond to standard therapy or standard or curative therapy does not exist or is not tolerable, and explore IN10018 monotherapy RP2D with the starting dose of IN10018 100mg QD per 3+3 design. The combination group will enroll patients who have disease progression within 3 months after at least first-line therapy, and explore IN10018+docetaxel RP2D with the starting dose of IN10018 100mg QD + docetaxel 75mg/m2 per 3+3 design. The dose expansion part will start after attaining the RP2D of IN10018 monotherapy and IN10018+docetaxel combination therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Anyang Tumor Hospital
Anyang, Henan, China
Henan Cancer Hospital
Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, China
Safety and tolerability in combination group
Number of patients with adverse event in combination group; Number of patients with laboratory abnormalities, abnormal vital signs and abnormal 12-lead ECG in combination group
Time frame: up to 24 months
DLTs in combination group
Number of patients with dose-limited toxicities (DLTs) in combination group
Time frame: 21 days
Phase II dose of IN10018 in combination with Docetaxel
Determine the recommended phase II dose (RP2D) of IN10018 in combination with Docetaxel
Time frame: up to 24 months
Safety and tolerability in IN10018 monotherapy group
Number of patients with adverse event in monotherapy group; Number of patients with laboratory abnormalities, abnormal vital signs and abnormal 12-lead ECG in monotherapy group
Time frame: up to 24 months
DLTs in IN10018 monotherapy group
Number of patients with dose-limited toxicities (DLTs) in monotherapy group
Time frame: up to 24 months
Objective response rate (ORR) per RECIST v1.1
Defined as the proportion of patients with complete response (CR) or partial response (PR).
Time frame: up to 24 months
Duration of objective response (DOR) per RECIST v1.1.
Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first
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The First Hospital of China Medical University
Shenyang, Liaoning, China
Shanghai East Hospital
Shanghai, Shanghai Municipality, China
The First Affiliated Hospital of XI 'AN Jiaotong University
Xi’an, Shanxi, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, China
Time frame: up to 24 months
Disease Control Rate (DCR) per RECIST v1.1.
Defined as the proportion of patients with CR, PR, or stable disease (SD)
Time frame: up to 24 months
Progression-free survival (PFS) per RECIST v1.1.
Defined as the time from start of study treatment to first documentation of disease progression or to death due to any cause, whichever comes first.
Time frame: up to 24 months
Overall survival (OS).
Defined as the time from the start of any study treatment to the date of death due to any cause.
Time frame: up to 30 months
Pharmacokinetics (PK):AUC
Area under the concentration-time curve (AUC).
Time frame: up to 24 months
Pharmacokinetics (PK):Cmax
PK: Maximum concentration (Cmax).
Time frame: up to 24 months
PK:Tmax
Time to Cmax (Tmax).
Time frame: up to 24 months
PK:Ctrough
Trough concentration (Ctrough).
Time frame: up to 24 months
PK:t1/2
Elimination half-life (t1/2).
Time frame: up to 24 months
PK:CL/F
apparent clearance (CL/F).
Time frame: up to 24 months
PK:Vd/F
Apparent volume of distribution (Vd/F).
Time frame: up to 24 months