HER2-negative Advanced Gastric Cancer
Conditions
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).
Interventions
DRUGLenvatinib plus taxane drugs
* 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
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to understand and the willingness to provide written informed consent. 2. Advanced gastric cancer diagnosed by histopathological or cytological examination, no uncontrollable pleural and ascites;. 3. Age no less than 18 years. 4. Life expectancy greater than 3 months. 5. According to the RECIST (Response Evaluation Criteria in Solid Tumors) standard, there must be measurable lesions. 6. Failed at the standard first-line therapy, microsatellite stable (MSS) or no mismatch repair missing(PMMR), HER2 negative. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 . 8. Adequate liver/bone marrow function. 9. Female subjects must meet the following conditions: infertility or fertility and use high-efficiency contraceptive measures. 10. 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
1. Previous use of lenvatinib or chemotherapy drugs in the regimen. 2. Pregnant or breast-feeding female, or not willing to take contraception measures during study. 3. Uncontrolled brain metastasis or mental illness. 4. Suffered from other uncured malignant tumors within the past 3 years or at the same time. 5. A history of active gastrointestinal bleeding within 3 months, incomplete obstruction or complete intestinal obstruction. 6. Uncontrollable high blood pressure are not suitable for enroll into the study. 7. Other uncontrolled diseases may cause abnormal death of the patient. 8. Untolerable liver/bone marrow function. 9. Factors that affect the administration of oral drugs (dysphagia, chronic diarrhea, complete intestinal obstruction, etc. 10. Previously allergic to the ingredients of the medicine in regimen. 11. Can't be followed up or obey protocol. 12. The investigator believes that it is not appropriate to participate in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose of lenvatinib | 4 weeks after the last administration | Maximum tolerated dose of lenvatinib in combination with single-agent chemotherapy |
| Adverse events | 4 weeks after the last administration | Incidence of DLT within 21 days of the first Lenvatinib application |
| Incidence of Treatment Related adverse events (TRAEs) | 4 weeks after the last administration | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
| Incidence of dose-limiting toxicities (DLTs) | 4 weeks after the last administration | 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) | 4 weeks after the last administration | Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | up to 12 months | Overall survival is defined as the time from signing ICF until death from any cause. |
| Objective response rate (ORR) | up to 12 months | 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 | up to 12 months | 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 | up to 12 months | 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 | up to 12 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Outcome | up to 8 weeks | 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. |
Countries
China
Contacts
Primary ContactYan Shi
Backup ContactHui Yang
Outcome results
None listed