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

Sponsor

Tianjin Medical University Cancer Institute and Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04267549

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase II study to evaluate the efficacy and safety of combination of sintilimab (PD-1 inhibitor) , apatinib and chemotherapy in unresectable advanced gastric cancer patients with oligo metastasis. This study was designed as single arm with fixed number of participants.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Stage	Drug: sintilimab Drug: apatinib Drug: S1 Drug: Nab paclitaxel	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

eligible patients will be given sintilimab, apatinib and xelox treatment each 3 weekseligible patients will be given sintilimab, apatinib and xelox treatment each 3 weeks

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2019

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment eligible patients will be given sintilimab (200mg, iv, q3w,)， apatinib (250mg/d， QD)，S1 （50mg PO，b.i.d d1-14 ）and nab-paclitaxel (260mg, iv, 3h, d1,q3w) for 3-6 cycles. If patients converted to surgery, then administer treatment post surgery upto 3cycles. Then give sintilimab and apatinib each 3 weeks for maintenance .	Drug: sintilimab sintilimab is checkpoint inhibitor via blocking PD-1 (programmed cell death-1) site of signaling. Other Names: Tyvyt Drug: apatinib a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI) Drug: S1 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). Drug: Nab paclitaxel Nab paclitaxel is a albumin-bound well tolerated paclitaxel than traditional paclitaxel

Arm

Intervention/Treatment

Experimental: treatment

eligible patients will be given sintilimab (200mg, iv, q3w,)， apatinib (250mg/d， QD)，S1 （50mg PO，b.i.d d1-14 ）and nab-paclitaxel (260mg, iv, 3h, d1,q3w) for 3-6 cycles. If patients converted to surgery, then administer treatment post surgery upto 3cycles. Then give sintilimab and apatinib each 3 weeks for maintenance .

Drug: sintilimab

sintilimab is checkpoint inhibitor via blocking PD-1 (programmed cell death-1) site of signaling.

Other Names:

Tyvyt

Drug: apatinib

a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI)

Drug: S1

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).

Drug: Nab paclitaxel

Nab paclitaxel is a albumin-bound well tolerated paclitaxel than traditional paclitaxel

Outcome Measures

Primary Outcome Measures

R0-surgery conversion rate [up to one year]
number of R0 surgery divide all participants (30pts)

Secondary Outcome Measures

adverse event [up to 30 days after last treatment administration]
all grades of adverse events, all grades of treatment related adverse events, serious of adverse events
R0 surgery rate [up to one year]
R0 surgery patient divide on all converted surgery patient
Overall response rate ( ORR) [up to 24 weeks from the first date of drugs administration]
the best over all response during treatment according to RECIST criteria
overall survival (OS) [up to two years]
median OS or OS rate in two years
Progression-free survival (PFS) [up to two years]
median PFS

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Hospital	Tianjin	Tianjin	China	300060

Sponsors and Collaborators

Tianjin Medical University Cancer Institute and Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Tianjin Medical University Cancer Institute and Hospital

ClinicalTrials.gov Identifier:

NCT04267549

Other Study ID Numbers:

E20207

First Posted:

Feb 13, 2020

Last Update Posted:

Jul 7, 2021

Last Verified:

Jun 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Tianjin Medical University Cancer Institute and Hospital

unresectable

metastatic gastric cancer

Additional relevant MeSH terms:

Stomach Neoplasms

Paclitaxel

Apatinib

Study Results

No Results Posted as of Jul 7, 2021