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

Apatinib Plus Sintilimab in Patients With Advanced Gastric Cancer

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

Study Overview

• Status: Unknown
• Conditions: Advanced Metastatic Gastric Cancer
• Intervention / Treatment: Drug: Apatinib Mesylate; Drug: Sintilimab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: JIE LIU, MD; Phone Number: 008613860632919; Email: dr2868@sina.com
• Study Contact Backup: Name: Nanfeng Fan, MD; Phone Number: 008613705007267; Email: Nanfeng_Fan@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Apatinib Mesylate; Apatinib 500mg qd, oral, taken half an hour after a meal; Other Names: Apatinib; Drug: Sintilimab; Sintilimab 200mg intravenously on day 1; Other Names: IBI308

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Duration of Response (DOR)	Time from date of first RECIST response to progressive disease [PD] or death	up to 12 months
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
Adverse events（AE）	Adverse events assessed using the NCI common toxicity criteria, version 4.01	up to 12 months

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital
• Investigators: Study Chair: Nanfeng Fan, MD, Fujian cancer hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: APAICI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No