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

Advanced Metastatic Gastric Cancer Clinical Trial

— ASGARD  

Official title:

Apatinib Plus Sintilimab in Patients With Advanced Gastric Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04089657
• Other study ID #: APAICI
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 1, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: September 2019
• Source: Fujian Cancer Hospital
• Contact: Nanfeng Fan, MD
• Phone: 008613705007267
• Email: Nanfeng_Fan[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Metastatic Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Apatinib Mesylate
Apatinib 500mg qd, oral, taken half an hour after a meal
• Sintilimab
Sintilimab 200mg intravenously on day 1

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Cancer Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease control rate(DCR)	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.	12 months
Secondary	Objective Response Rate (ORR)	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.	12 months
Secondary	Overall survival (OS)	Overall survival (OS) was calculated from the date of initial treatment with apatinib to the date of death due to any cause.	up to 12 months
Secondary	Duration of Response (DOR)	Time from date of first RECIST response to progressive disease [PD] or death	up to 12 months
Secondary	Progression Free Survival (PFS)	PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause.	up to 12 months
Secondary	Adverse events(AE)	Adverse events assessed using the NCI common toxicity criteria, version 4.01	up to 12 months