Advanced Metastatic Gastric Cancer
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of Apatinib combined with PD-1 antibody Sintilimab for for Chemotherapy-Refractory Advanced Metastatic Gastric Cancer
Detailed description
Patients with advanced gastric cancer (AGC) can be treated with multiple lines of chemotherapy. After second-line treatment some patients may receive third- and subsequent lines of chemotherapy if their performance status is well-preserved and they are willing to receive subsequent active treatments. Apatinib is a small-molecule VEGFR-2 tyrosine kinase inhibitor approved by the CFDA for the treatment of advanced gastric cancer. In a phase III trial, apatinib significantly improved PFS and OS compared with placebo, but the clinical benefit was modest. As a result of toxicity, 850 mg/day Apatinib may cause dose reduction and delay in some patients ,which also caused some doubts. Therefore, it is a reasonable treatment strategy by reducing the dose and combining it with another low-toxic drug to achieve similar or better effects. Some studies have shown that the combination of targeted therapy and immunotherapy may be effective in solid tumor. Sintilimab (IBI308) is a monoclonal antibody targeting programmed death-1 (PD-1). So, the investigators designed an open-label, single-arm, phase II clinical study to evaluate the efficacy and safety of apatinib combined with Sintilimab in Chemotherapy-Refractory Advanced Metastatic Gastric Cancer.
Interventions
DRUGApatinib Mesylate
Apatinib 500mg qd, oral, taken half an hour after a meal
DRUGSintilimab
Sintilimab 200mg intravenously on day 1
Sponsors
Fujian Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age between 20-75 years old * Has histologically confirmed diagnosis of unresectable locally advanced,recurrent or metastatic gastric or GEJ adenocarcinoma * Life expectancy of more than 3 months * Eastern Cooperative Oncology Group (ECOG) performance status was 0 - 1 * Have failed for at least 2 lines of chemotherapy * At least 3 weeks from previous chemotherapy at first dose of trial drug * Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTC) (except for the laboratory values) * Failure of prior palliative chemotherapy/chemotherapies (at least one irinotecan- or cisplatin-based). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment. * At least one measurable lesion defined by RECIST 1.1 as determined by investigator assessment. * Has adequate organ function * At least 4 weeks from any major surgery (at first dose of trial drug) * Patients must be able to swallow apatinib
Exclusion criteria
* In the past, participants have received anti PD-1, anti PD-L1 or anti PD-L2 drugs or drugs targeting another stimulation or synergistic inhibition of T cell receptors (such as Cytotoxic T-Lymphocyte Antigen 4 \[CTLA-4\] and CD137) * Other co-existing malignancies or malignancies diagnosed within the last 5 years(except cured cutaneum carcinoma or carcinoma in situs of cervix) * Less than 4 weeks from the last clinical trial * Active and uncontrollable bleeding from gastrointestinal tract * Known history of QT interval prolongation, ongoing QT prolongation (\> 450 msec for males or \> 470 msec for females), any cardiac ventricular dysrhythmias, atrial fibrillation of any grade * Hypertension that cannot be controlled by medications (\> 140/90 mmHg despite optimal medical therapy) * Abnormal Coagulation (INR\>1.5、APTT\>1.5 UNL), with tendency of bleed; * Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); * Active uncontrolled infection * Known human immunodeficiency virus (HIV) infection * Symptomatic central nervous metastasis and/or cancerous meningitis * Known allergic/hypersensitivity reaction to any of the components of the treatment; or known drug abuse/alcohol abuse * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate(DCR) | 12 months | The percentage of patients who have achieved complete response, partial response and stable disease,evaluated by RECIST, confirmed at least 4 weeks following the date of the initial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 12 months | The percentage of patients who achieve complete response or partial response,evaluated by RECIST, confirmed at least 4 weeks following the date of the initial response. |
| Overall survival (OS) | up to 12 months | Overall survival (OS) was calculated from the date of initial treatment with apatinib to the date of death due to any cause. |
| Duration of Response (DOR) | up to 12 months | Time from date of first RECIST response to progressive disease \[PD\] or death |
| Progression Free Survival (PFS) | up to 12 months | PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause. |
| Adverse events（AE） | up to 12 months | Adverse events assessed using the NCI common toxicity criteria, version 4.01 |
Contacts
Primary ContactNanfeng Fan, MD
Backup ContactJIE LIU, MD
Outcome results
None listed