IN10018 Monotherapy or in Combination With Docetaxel in Gastric or GEJ Adenocarcinoma

Gastric Cancer Clinical Trial

Official title:

A Phase I, Open-label Clinical Trial to Evaluate Safety, Tolerability, Antitumor Activities and Pharmacokinetics of IN10018 as Mono or Combination Therapy in Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05327231
• Other study ID #: IN10018-003
• Status: Completed
• Phase: Phase 1
• Start date: July 9, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: September 2022
• Source: InxMed (Shanghai) Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 31, 2022
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 1.Has histologically or cytologically confirmed diagnosis of locally advanced and/or metastatic gastric or GEJ adenocarcinoma.
• For monotherapy, participants need to be failed to respond to standard therapy or standard or curative therapy does not exist or is not tolerable.
• For combination therapy, participants need to have disease progression within 3 months after at least first-line therapy.
• 2.Has at least one measurable tumor lesion per RECIST 1.1.
• 3.Has an ECOG performance status of 0 or 1.
• 4.Estimated life expectancy is more than 3 months.
• 5.Adequate organ and bone marrow functions.
• 6.Has been fully informed and provided written informed consent for the study

Exclusion Criteria:

• 1.Has other histological types other than adenocarcinoma.
• 2.For participants with HER2/neu positive tumors or have an unknown tumor status, need

to match the following:

• If HER2/neu positive, participant must have documentation of disease progression on trastuzumab or other anti-HER2/neu therapy.
• Participants with unknown status must have their HER2/neu status determined locally. If HER2/neu-negative, the participant will be eligible. If HER2/neu-positive, the participant must have documentation of disease progression on trastuzumab or other anti-HER2/neu therapy.
• 3.Has had disease progression after docetaxel/paclitaxel containing treatment (combination therapy only).
• 4.Has received prior systemic therapies (i.e. chemotherapy, biotherapy, endocrinotherapy, and immunotherapy) within 4 weeks prior to start of study treatment.
• 5.Has received prior radiotherapy within 2 weeks prior to start of study treatment.
• 6.Has severe allergy or hypersensitivity to IN10018 and/or docetaxel, or any components used in their preparation or has contraindication for taxane therapy. For participants in monotherapy group, only restriction to IN10018 applies.
• 7.Has severe renal disease or impaired renal function.
• 8.Has an active infection requiring systemic therapy within 2 weeks prior to start of study treatment.
• 9.Has a history or current evidence of interstitial lung disease.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer

Intervention

Drug:
• IN10018
IN10018 orally once daily at approximately the same time each day, to ensure a dose interval of approximately 24 hours.
• Docetaxel
Docetaxel 75mg/m2 every 21 days a cycle.

Locations

Country	Name	City	State
China	Anyang Tumor Hospital	Anyang	Henan
China	The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	Shanghai East Hospital	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of XI 'AN Jiaotong University	Xi'an	Shanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
InxMed (Shanghai) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	up to 24 months
Primary	DLTs in combination group	Number of patients with dose-limited toxicities (DLTs) in combination group	21 days
Primary	Phase II dose of IN10018 in combination with Docetaxel	Determine the recommended phase II dose (RP2D) of IN10018 in combination with Docetaxel	up to 24 months
Secondary	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	up to 24 months
Secondary	DLTs in IN10018 monotherapy group	Number of patients with dose-limited toxicities (DLTs) in monotherapy group	up to 24 months
Secondary	Objective response rate (ORR) per RECIST v1.1	Defined as the proportion of patients with complete response (CR) or partial response (PR).	up to 24 months
Secondary	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	up to 24 months
Secondary	Disease Control Rate (DCR) per RECIST v1.1.	Defined as the proportion of patients with CR, PR, or stable disease (SD)	up to 24 months
Secondary	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.	up to 24 months
Secondary	Overall survival (OS).	Defined as the time from the start of any study treatment to the date of death due to any cause.	up to 30 months
Secondary	Pharmacokinetics (PK):AUC	Area under the concentration-time curve (AUC).	up to 24 months
Secondary	Pharmacokinetics (PK):Cmax	PK: Maximum concentration (Cmax).	up to 24 months
Secondary	PK:Tmax	Time to Cmax (Tmax).	up to 24 months
Secondary	PK:Ctrough	Trough concentration (Ctrough).	up to 24 months
Secondary	PK:t1/2	Elimination half-life (t1/2).	up to 24 months
Secondary	PK:CL/F	apparent clearance (CL/F).	up to 24 months
Secondary	PK:Vd/F	Apparent volume of distribution (Vd/F).	up to 24 months