search
Back to results

Conversion Therapy of Sintilimab in Combination With Apatinib and Chemotherapy in Stage IV Gastric Cancer

Primary Purpose

Gastric Cancer Stage IV

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
sintilimab
apatinib
S1
Nab paclitaxel
Sponsored by
Tianjin Medical University Cancer Institute and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer Stage IV focused on measuring PD-1 inhibitor, conversion therapy

Eligibility Criteria

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

Inclusion Criteria:

  • 18-70 years old;
  • gastroscopy and pathology (histologically/cytologically ) confirmed local advanced or oligo-metastatic gastric adenocarcinoma;
  • unresectable;
  • ≥3m life expectancy；
  • must have at least 1 measurable lesion using RECIST v1.1 criteria；
  • adequate organ function
  • pregnant test negative of females of childbearing potential , and willing to use adequate contraception
  • written Informed Consensus Form

Exclusion Criteria:

  • prior use of any checkpoint inhibitor treatment, including with no limited to PD-1, programmed cell death ligand-1(PDL-1), CTLA4 etc;
  • patients with central nervous system, lung, or bone metastasis;
  • Her 2 positive with willing to use herceptin treatment;
  • prior active autoimmune disease or history of autoimmune disease;
  • patients with other malignant tumor
  • clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) < 50%;
  • not controlled hypertension;
  • prior systemic treatment to metastatic disease；
  • previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency;
  • patients with or previous with serious hemorrhage ;
  • active infection or an unexplained fever;
  • objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, pulmonary function damaged seriously etc.
  • history of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or active hepatitis ;
  • patients who may receive vaccination during study period;
  • mental disorders history, or psychotropic drug abuse history;
  • unable to orally administration;

Sites / Locations

  • Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment

Arm Description

Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m^2 iv for 3h; with peritoneal metastases: 200mg/m^2 iv plus 60mg/m^2 ip; day 1) every 3 weeks for at least 3 cycles. The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles. Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment. Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.

Outcomes

Primary Outcome Measures

R0-surgery conversion rate
The proportion of participants who underwent R0 surgery among all participants.

Secondary Outcome Measures

objective response rate (ORR)
The proportion of participants who achieved complete response(CR) or partial response(PR) per Response Evaluation Criteria in Solid Tumors criteria (RECIST v1.1).
disease control rate (DCR)
The proportion of participants who achieved CR, PR or stable disease(SD) per RECIST v1.1.
conversion rate
The proportion of participants who underwent surgery among all participants.
overall survival (OS)
The time from the first dose of the study treatment to death from any cause.
event-free survival (EFS)
The time from the first dose of the study treatment to any of the following events: progression of disease, local or distant recurrence, or death due to any cause.
Treatment-Related Adverse Events (TRAEs)
The grade and proportion of participants who experienced TRAEs per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
surgery-related complications
Incidence and grade of surgery-related complications as assessed byper the Clavien-Dindo classification

Full Information

First Posted
January 21, 2020
Last Updated
July 3, 2023
Sponsor
Tianjin Medical University Cancer Institute and Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04267549
Brief Title
Conversion Therapy of Sintilimab in Combination With Apatinib and Chemotherapy in Stage IV Gastric Cancer
Official Title
Efficacy and Safety of Conversion Therapy With Sintilimab in Combination With Chemotherapy and Apatinib in Patients With Stage IV Gastric Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
August 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a single-arm, phase II study aiming to evaluate the feasibility and efficacy of sintilimab (PD-1 inhibitor) in combination of apatinib and two-drug chemotherapy (S-1 plus nab-paclitaxel) as conversion therapy in patients with stage IV gastric cancer in China.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer Stage IV
Keywords
PD-1 inhibitor, conversion therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
eligible patients will be given treatment of sintilimab, apatinib and chemotherapy (nab-paclitaxel) every 3 weeks
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
treatment
Arm Type
Experimental
Arm Description
Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m^2 iv for 3h; with peritoneal metastases: 200mg/m^2 iv plus 60mg/m^2 ip; day 1) every 3 weeks for at least 3 cycles. The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles. Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment. Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
Intervention Type
Drug
Intervention Name(s)
sintilimab
Other Intervention Name(s)
Tyvyt
Intervention Description
a checkpoint inhibitor via blocking PD-1 (programmed cell death-1) site of signaling.
Intervention Type
Drug
Intervention Name(s)
apatinib
Intervention Description
a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI)
Intervention Type
Drug
Intervention Name(s)
S1
Intervention Description
S-1 is an oral fluoropyrimidine consisting of tegafur (a prodrug that is converted to fluorouracil, mainly in liver microsomes but also in tumour tissue), gimeracil (an inhibitor of dihydropyrimidine dehydrogenase, which degrades 5-FU), and oteracil (which inhibits the phosphorylation of 5-FU in the gastrointestinal tract, thereby reducing the toxic effects of 5-FU in the intestinum).
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
Nab paclitaxel is a albumin-bound well tolerated paclitaxel than traditional paclitaxel
Primary Outcome Measure Information:
Title
R0-surgery conversion rate
Description
The proportion of participants who underwent R0 surgery among all participants.
Time Frame
up to one year
Secondary Outcome Measure Information:
Title
objective response rate (ORR)
Description
The proportion of participants who achieved complete response(CR) or partial response(PR) per Response Evaluation Criteria in Solid Tumors criteria (RECIST v1.1).
Time Frame
up to one year
Title
disease control rate (DCR)
Description
The proportion of participants who achieved CR, PR or stable disease(SD) per RECIST v1.1.
Time Frame
up to one year
Title
conversion rate
Description
The proportion of participants who underwent surgery among all participants.
Time Frame
up to one year
Title
overall survival (OS)
Description
The time from the first dose of the study treatment to death from any cause.
Time Frame
up to two years
Title
event-free survival (EFS)
Description
The time from the first dose of the study treatment to any of the following events: progression of disease, local or distant recurrence, or death due to any cause.
Time Frame
up to two years
Title
Treatment-Related Adverse Events (TRAEs)
Description
The grade and proportion of participants who experienced TRAEs per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Time Frame
from the first day of treatment until 1 month after the end of treatment
Title
surgery-related complications
Description
Incidence and grade of surgery-related complications as assessed byper the Clavien-Dindo classification
Time Frame
from the day of surgery to 30 days postoperatively
Other Pre-specified Outcome Measures:
Title
pathological response
Description
Pathological response of the primary tumor was graded according to tumor regression grade (TRG) as follows: 0. (CR), no viable cancer cells, including lymph nodes; 1. (near CR), single cells or rare small groups of cancer cells; 2. (PR), residual cancer cells with evident tumor regression but more than single cells or rare small groups of cancer cells; and 3. (poor or no response), extensive residual cancer with no evident tumor regression.
Time Frame
up to one year after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: gastric adenocarcinoma confirmed by gastroscopy and pathology (histologically/cytologically ) ; life expectancy of ≥3-month； unresectable patients who were initially diagnosed as stage IV (clinical stage, American Joint Committee on Cancer 8th edition); Eastern Cooperative Oncology Group performance status: 0-1; must have at least 1 of the following unresectable factors indicated by CT, MRI or positron emission tomography(PET)-CT: N3 lymphatic metastasis; Extensive or bulky lymph nodes; T4b; Hepatic metastasis: ≤5 lesions, total diameter of ≤8cm; Peritoneal metastasis (CY1, P1); Kukernburg tumor; adequate organ function; pregnant test negative of females of childbearing potential , and willing to use adequate contraception; written Informed Consensus Form; Exclusion Criteria: prior use of any checkpoint inhibitor treatment, including PD-1, programmed cell death ligand-1(PDL-1), CTLA4 etc; Her-2 positive with willing to use herceptin treatment; prior active autoimmune disease or history of autoimmune disease; clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) < 50%; not controlled hypertension; prior systemic treatment to metastatic disease； previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency; history of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or active hepatitis ; patients who may receive vaccination during study period; mental disorders history, or psychotropic drug abuse history; unable to orally administration;
Facility Information:
Facility Name
Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China

12. IPD Sharing Statement

Learn more about this trial

Conversion Therapy of Sintilimab in Combination With Apatinib and Chemotherapy in Stage IV Gastric Cancer

We'll reach out to this number within 24 hrs