Back to resultsLenvatinib With Taxane Drugs Treatment for Advanced Gastric Cancer
Primary Purpose
HER2-negative Advanced Gastric Cancer
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Lenvatinib plus taxane drugs
Sponsored by
About this trial
This is an interventional treatment trial for HER2-negative Advanced Gastric Cancer
Eligibility Criteria
Inclusion Criteria:
- Ability to understand and the willingness to provide written informed consent.
- Advanced gastric cancer diagnosed by histopathological or cytological examination, no uncontrollable pleural and ascites;.
- Age no less than 18 years.
- Life expectancy greater than 3 months.
- According to the RECIST (Response Evaluation Criteria in Solid Tumors) standard, there must be measurable lesions.
- Failed at the standard first-line therapy, microsatellite stable (MSS) or no mismatch repair missing(PMMR), HER2 negative.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 .
- Adequate liver/bone marrow function.
- Female subjects must meet the following conditions: infertility or fertility and use high-efficiency contraceptive measures.
- Male subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for 3 months following the last dose of the study cell infusion. Moreover, all men are absolutely prohibited from donating sperm within 1 year after receiving the last study treatment infusion.
Exclusion Criteria:
- Previous use of lenvatinib or chemotherapy drugs in the regimen.
- Pregnant or breast-feeding female, or not willing to take contraception measures during study.
- Uncontrolled brain metastasis or mental illness.
- Suffered from other uncured malignant tumors within the past 3 years or at the same time.
- A history of active gastrointestinal bleeding within 3 months, incomplete obstruction or complete intestinal obstruction.
- Uncontrollable high blood pressure are not suitable for enroll into the study.
- Other uncontrolled diseases may cause abnormal death of the patient.
- Untolerable liver/bone marrow function.
- Factors that affect the administration of oral drugs (dysphagia, chronic diarrhea, complete intestinal obstruction, etc.
- Previously allergic to the ingredients of the medicine in regimen.
- Can't be followed up or obey protocol.
- The investigator believes that it is not appropriate to participate in the trial.
Sites / Locations
- Ruijin HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lenvatinib with taxane drugs treatment for advanced gastric cancer
Arm Description
Experimental: Lenvatinib plus taxane drugs The subjects in this arm will receive a Lenvatinib combined with single-agent taxanes therapy. A standard dose of chemotherapy: paclitaxel 135mg/m2 every 3 weeks or docetaxel 75mg/m2 every 3 weeks will be administrated. Lenvatinib is exploring four doses of 4mg, 8mg, 12mg, and 16mg, orally once a day every 3 weeks. In the first cycle, lenvatinib was administered 5 days before chemotherapy，once a day. Chemotherapy lasts up to 6 cycles, and lenvatinib continues to be administered until the disease progresses, intolerable side effects, or death. Subjects will be enrolled serially. For subject safety, the preceding subject must have completed therapy and there is no obvious DLT within 21 days before the next subject can be treated. Interventions: Drug: Paclitaxel or Docetaxel Drug: Lenvatinib
Outcomes
Primary Outcome Measures
Adverse events
Incidence of DLT within 21 days of the first Lenvatinib application
Incidence of Treatment Related adverse events (TRAEs)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Incidence of dose-limiting toxicities (DLTs)
All patients who have received at least one dose of treatment will be included in the safety analysis. Number of participants with dose-limiting toxicities as assessed by CTCAE v5.0
Incidence of Treatment Emergent Adverse Event (TEAEs)
Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0
Maximum tolerated dose of lenvatinib
Maximum tolerated dose of lenvatinib in combination with single-agent chemotherapy
Secondary Outcome Measures
Objective response rate (ORR)
Objective Response Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR) based on RECIST v1.1.
Disease control rate (DCR) based on the researcher's evaluation
Disease control Rate is defined as the percentage of patients with a documented complete response or partial response or stable disease (CR + PR+SD) based on RECIST v1.1.
Duration of Remission (DOR) based on the researcher's evaluation
The duration of remission (DOR) is defined as the time interval between the subject's first recording of disease remission to the first recording of disease progression.
Progression-free survival (PFS) based on the researcher's evaluation
Progression-free survival (PFS) is defined as the time interval from the first treatment of the subject to the first recording of disease progression or death due to any cause, whichever occurs first.
Overall survival (OS)
Overall survival is defined as the time from signing ICF until death from any cause.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05171530
Brief Title
Lenvatinib With Taxane Drugs Treatment for Advanced Gastric Cancer
Official Title
An Exploratory Clinical Study of Lenvatinib Combined With Single-agent Taxanes as Second-line Therapy for the Treatment of HER2-negative Advanced Gastric Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 5, 2022 (Anticipated)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The goal of this clinical trial is to study the safety and efficacy of lenvatinib combined with single-agent taxanes therapy in patients with HER2-negative advanced gastric cancer that have failed at the standard first-line therapy.
Detailed Description
This study is being conducted to establish safety and preliminary efficacy of Lenvatinib plus taxane drugs treatment for HER2-negative advanced gastric cancer after failure of first-line treatment.
The study will adopt the "3+3" dose escalation design. All patients received a standard dose of chemotherapy: paclitaxel 135mg/m2 every 3 weeks or docetaxel 75mg/m2 every 3 weeks. Lenvatinib is exploring four doses of 4mg, 8mg, 12mg, and 16mg, orally once a day every 3 weeks. In the first cycle, lenvatinib was administered 5 days before chemotherapy，once a day. Chemotherapy lasts up to 6 cycles, and lenvatinib continues to be administered until the disease progresses, intolerable side effects, or death.
In order to avoid the possible ineffectiveness caused by the patient being exposed to low doses, the initial dose of 4 mg was enrolled in 1 patient. If there is no obvious dose-limiting toxicity (DLT) after the first dose, the dose escalation adopts a "3+3" method from the 8mg dose: if none of the 3 subjects in the previous dose group has a DLT within 21 days, the next dose study will be carried out; if one subject in the group has DLT occurs, then 3 additional subjects should be added to the dose group; if the 3 subjects have 1 or more DLTs, the trial terminated and the previous dose was regarded as the maximum tolerated dose (MTD).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-negative Advanced Gastric Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lenvatinib with taxane drugs treatment for advanced gastric cancer
Arm Type
Experimental
Arm Description
Experimental: Lenvatinib plus taxane drugs The subjects in this arm will receive a Lenvatinib combined with single-agent taxanes therapy. A standard dose of chemotherapy: paclitaxel 135mg/m2 every 3 weeks or docetaxel 75mg/m2 every 3 weeks will be administrated. Lenvatinib is exploring four doses of 4mg, 8mg, 12mg, and 16mg, orally once a day every 3 weeks. In the first cycle, lenvatinib was administered 5 days before chemotherapy，once a day. Chemotherapy lasts up to 6 cycles, and lenvatinib continues to be administered until the disease progresses, intolerable side effects, or death.
Subjects will be enrolled serially. For subject safety, the preceding subject must have completed therapy and there is no obvious DLT within 21 days before the next subject can be treated.
Interventions:
Drug: Paclitaxel or Docetaxel
Drug: Lenvatinib
Intervention Type
Drug
Intervention Name(s)
Lenvatinib plus taxane drugs
Intervention Description
Drug: Paclitaxel Dose: 135mg/m2 Other Name: PTX
Drug: Docetaxel Dose: 75mg/m2 Other Name: FA
Drug: Lenvatinib Dose: 4mg, 8mg, 12mg,16mg Other Name: FA
Primary Outcome Measure Information:
Title
Adverse events
Description
Incidence of DLT within 21 days of the first Lenvatinib application
Time Frame
4 weeks after the last administration
Title
Incidence of Treatment Related adverse events (TRAEs)
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
4 weeks after the last administration
Title
Incidence of dose-limiting toxicities (DLTs)
Description
All patients who have received at least one dose of treatment will be included in the safety analysis. Number of participants with dose-limiting toxicities as assessed by CTCAE v5.0
Time Frame
4 weeks after the last administration
Title
Incidence of Treatment Emergent Adverse Event (TEAEs)
Description
Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0
Time Frame
4 weeks after the last administration
Title
Maximum tolerated dose of lenvatinib
Description
Maximum tolerated dose of lenvatinib in combination with single-agent chemotherapy
Time Frame
4 weeks after the last administration
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Objective Response Rate is defined as the percentage of patients with a documented complete response or partial response (CR + PR) based on RECIST v1.1.
Time Frame
up to 12 months
Title
Disease control rate (DCR) based on the researcher's evaluation
Description
Disease control Rate is defined as the percentage of patients with a documented complete response or partial response or stable disease (CR + PR+SD) based on RECIST v1.1.
Time Frame
up to 12 months
Title
Duration of Remission (DOR) based on the researcher's evaluation
Description
The duration of remission (DOR) is defined as the time interval between the subject's first recording of disease remission to the first recording of disease progression.
Time Frame
up to 12 months
Title
Progression-free survival (PFS) based on the researcher's evaluation
Description
Progression-free survival (PFS) is defined as the time interval from the first treatment of the subject to the first recording of disease progression or death due to any cause, whichever occurs first.
Time Frame
up to 12 months
Title
Overall survival (OS)
Description
Overall survival is defined as the time from signing ICF until death from any cause.
Time Frame
up to 12 months
Other Pre-specified Outcome Measures:
Title
Exploratory Outcome
Description
Dynamic contrast-enhanced ultrasound (DCE-US) was used to evaluate the the efficacy of anti-angiogenic therapy. Wash-in area under the curve (WiAUC) were quantitatively by DCE-US before the chemotherapy(d-4), d1 and 42 days after chemotherapy.
Time Frame
up to 8 weeks
Title
Exploratory Outcome
Description
Mass spectrometry flow cytometry was used to detect the ratio and number of CD8+T cells on d0 and d42 after Lenvatinib therapy, and evaluates the correlation between changes in the immune microenvironment and the efficacy.
Time Frame
up to 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability to understand and the willingness to provide written informed consent.
Advanced gastric cancer diagnosed by histopathological or cytological examination, no uncontrollable pleural and ascites;.
Age no less than 18 years.
Life expectancy greater than 3 months.
According to the RECIST (Response Evaluation Criteria in Solid Tumors) standard, there must be measurable lesions.
Failed at the standard first-line therapy, microsatellite stable (MSS) or no mismatch repair missing(PMMR), HER2 negative.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 .
Adequate liver/bone marrow function.
Female subjects must meet the following conditions: infertility or fertility and use high-efficiency contraceptive measures.
Male subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for 3 months following the last dose of the study cell infusion. Moreover, all men are absolutely prohibited from donating sperm within 1 year after receiving the last study treatment infusion.
Exclusion Criteria:
Previous use of lenvatinib or chemotherapy drugs in the regimen.
Pregnant or breast-feeding female, or not willing to take contraception measures during study.
Uncontrolled brain metastasis or mental illness.
Suffered from other uncured malignant tumors within the past 3 years or at the same time.
A history of active gastrointestinal bleeding within 3 months, incomplete obstruction or complete intestinal obstruction.
Uncontrollable high blood pressure are not suitable for enroll into the study.
Other uncontrolled diseases may cause abnormal death of the patient.
Untolerable liver/bone marrow function.
Factors that affect the administration of oral drugs (dysphagia, chronic diarrhea, complete intestinal obstruction, etc.
Previously allergic to the ingredients of the medicine in regimen.
Can't be followed up or obey protocol.
The investigator believes that it is not appropriate to participate in the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Shi
Phone
13810561979
Email
sy_rjh@aliyun.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Yang
Phone
15216660039
Email
yanghui0182@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yan Shi
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Shi
Phone
13810561979
Email
sy_rjh@aliyun.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Lenvatinib With Taxane Drugs Treatment for Advanced Gastric Cancer
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