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

Primary Purpose

Advanced Metastatic Gastric Cancer

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Apatinib Mesylate

Sintilimab

About this trial

This is an interventional treatment trial for Advanced Metastatic Gastric Cancer

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Apatinib+Sintilimab

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Duration of Response (DOR)

Time from date of first RECIST response to progressive disease [PD] or death

Progression Free Survival (PFS)

PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause.

Adverse events（AE）

Adverse events assessed using the NCI common toxicity criteria, version 4.01

Full Information

NCT ID

NCT04089657

First Posted

September 10, 2019

Last Updated

September 12, 2019

Sponsor

Fujian Cancer Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04089657

Brief Title

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

Acronym

ASGARD

Official Title

Apatinib Plus Sintilimab in Patients With Advanced Gastric Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Unknown status

Study Start Date

December 1, 2019 (Anticipated)

Primary Completion Date

December 1, 2020 (Anticipated)

Study Completion Date

December 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fujian Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Metastatic Gastric Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Apatinib+Sintilimab

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Apatinib Mesylate

Other Intervention Name(s)

Apatinib

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Sintilimab

Other Intervention Name(s)

IBI308

Intervention Description

Sintilimab 200mg intravenously on day 1

Primary Outcome Measure Information:

Title

Disease control rate(DCR)

Description

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.

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

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.

Time Frame

12 months

Title

Overall survival (OS)

Description

Overall survival (OS) was calculated from the date of initial treatment with apatinib to the date of death due to any cause.

Time Frame

up to 12 months

Title

Duration of Response (DOR)

Description

Time from date of first RECIST response to progressive disease [PD] or death

Time Frame

up to 12 months

Title

Progression Free Survival (PFS)

Description

PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause.

Time Frame

up to 12 months

Title

Adverse events（AE）

Description

Adverse events assessed using the NCI common toxicity criteria, version 4.01

Time Frame

up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nanfeng Fan, MD

Phone

008613705007267

Nanfeng_Fan@sina.com

First Name & Middle Initial & Last Name or Official Title & Degree

JIE LIU, MD

Phone

008613860632919

dr2868@sina.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nanfeng Fan, MD

Organizational Affiliation

Fujian Cancer Hospital

Official's Role

Study Chair

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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