Apatinib Plus Sintilimab in Advanced Gastric Cancer Refractory to at Least Two Previous Chemotherapy Regimens

NCT ID: NCT04089657

Last Updated: 2019-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-01
• Study Completion Date: 2021-12-01

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.

Conditions

Advanced Metastatic Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Apatinib+Sintilimab

Apatinib 500mg qd p.o and Sintilimab 200mg intravenously on day 1 every 3 weeks until disease progression or intolerable toxicity or patients withdrawal of consent

Group Type: EXPERIMENTAL

Apatinib Mesylate

Intervention Type: DRUG

Apatinib 500mg qd, oral, taken half an hour after a meal

Sintilimab

Intervention Type: DRUG

Sintilimab 200mg intravenously on day 1

Interventions

Apatinib Mesylate

Apatinib 500mg qd, oral, taken half an hour after a meal

Intervention Type: DRUG

Sintilimab

Sintilimab 200mg intravenously on day 1

Intervention Type: DRUG

Other Intervention Names

Apatinib; IBI308

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nanfeng Fan, MD

Role: STUDY_CHAIR

Fujian Cancer Hospital

Central Contacts

Nanfeng Fan, MD

Role: CONTACT

Nanfeng_Fan@sina.com

008613705007267

JIE LIU, MD

Role: CONTACT

dr2868@sina.com

008613860632919

Other Identifiers

APAICI

Identifier Type: -

Identifier Source: org_study_id