Clinical trial NCT04089657: Apatinib Plus Sintilimab in Advanced Gastric Cancer Refractory to at Least Two Previous Chemotherapy Regimens
Official title: Apatinib Plus Sintilimab in Patients With Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Metastatic Gastric Cancer
Lead sponsor: Fujian Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2019-09-13
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease control rate(DCR)
timeFrame: 12 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 12 months
measure: Overall survival (OS)
timeFrame: up to 12 months
measure: Duration of Response (DOR)
timeFrame: up to 12 months
measure: Progression Free Survival (PFS)
timeFrame: up to 12 months
measure: Adverse events（AE）
timeFrame: up to 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Fujian Cancer Hospital
name: Nanfeng Fan, MD
role: STUDY_CHAIR
References: