Back to resultsNeoadjuvant Immunotherapy for Resectable Gastric Cancer
Primary Purpose
Gastric Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
SHR1210
Apatinib
S1
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer
Eligibility Criteria
Inclusion Criteria:
- Aged 18-70 years old, both genders, histologically documented gastric cancer.
- Newly diagnosed locally advanced, potentially resectable disease without any prior antitumor treatment
- clinically diagnosed stage T3-4bN+M0 according to ultrasound endoscopy or enhanced CT/MRI scan.
- Eligible and reasonably suitable for potentially curative resection
- Written (signed) informed consent.
- Pathological tissue available
- ECOG: 0-1.
- Adequate organ function.
- Willingness to provide blood and tissue samples for research purposes.
- Good compliance with the study procedures, including lab and auxiliary examination and treatment.
- Female patients should not be pregnant or breast feeding.
- Agree to take contraception measures during treatment and in 120 days after last dose of SHR-1210.
- Life expectancy of at least 6 months.
Exclusion Criteria:
- Patients with distant metastasis.
- History of chemotherapy, radiation, immunotherapy, or radical resection of gastric cancer.
- patients with active autoimmune disease or history of refractory autoimmune disease.
- patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ.
- uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
- patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
- perforation / fistula of GI tract in 6 months before recruitment.
- pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis, pulmonary fibrosis, acute pulmonary disease.
- uncontrollable systemic diseases, including diabetes, hypertension etc.
- severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB or HIV, etc.
- patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV RNA.
- patients with any cardiovascular risk factors below: （1）cardiac chest pain occurring in 28 days before recruitment, defined as moderate pain that limits daily activity.
（2）pulmonary embolism with symptoms occurring in 28 days before recruitment. （3）acute myocardial infarction occurring in 6 months before recruitment. （4）any history of heart failure reaching grade 3/4 of NYHA in 6 months before recruitment.
（5）ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, or accompanied by supraventricular tachyarrhythmias requiring medical treatment.
（6）cerebrovascular accident within 6 months before recruitment. 14. patients with peripheral neuropathy NCI CTC AE grade 1, except those with only deep tendon reflex disappearing.
15. moderate or severe renal injury [creatinine clearance rate≤50 ml/min (according to Cockcroft & Gault equation)], or Scr>ULN.
16. dipyrimidine dehydrogenase (DPD) deficiency. 17. allergic to any drug in this study. 18. history of allogeneic stem cell transplantation or organ transplantation. 19. use of steroids (dosage>10mg/d prednisone) or other systemic immune suppressive therapy in 14 days before recruitment, except patients treated with regimens below: a. steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local application with little systemic absorption; c. short -term (≤ 7 days) steroids for preventing allergy or vomiting.
20. vaccinated with live vaccine in 4 weeks before recruitment. 21. for patients with uncontrolled epilepsy, CNS diseases or history of mental disorder, researchers should evaluate whether their diseases will impede their signing of informed consent or compliance of treatment.
22. existing of potential situation which will impede drug administration or affect toxicity analysis or alcohol/ drug abuse.
Sites / Locations
- Qilu hospital of Shandong univertisyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Neoadjuvant immunotherapy with PD-1
Neoadjuvant immunotherapy with PD-1+apatinib
Neoadjuvant immunotherapy with PD-1+apatinib+S1
Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin
Arm Description
Outcomes
Primary Outcome Measures
Pathological remission rate (PRR) rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
The pathological response was calculated according to the proportion of residual viable tumor cells in the tumor bed. Complete pathological response (CPR) was defined as no residue tumor cells. Major pathological response (MPR) was defined as less than 10% residue tumor cells.
Immunotherapy-related biomarkers
To evaluate the relationship between tumor pathological remission and immunotherapy related biomarkers, including tumor genome, tumor microenvironment and host immune system response biomarkers.
Secondary Outcome Measures
objective response rate (ORR) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1. However, responses do not require confirmation according to RECIST v 1.1. ORR was evaluated by chest, abdominal & pelvic CT/MRI.
progression free survival (PFS)of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
PFS is defined as time interval from recruitment to tumor progression. Tumor progression is defined as below: 1) tumor re-occurrence, 2) death, 3) censoring, and 4) beginning to use any other anti-tumor medicines.
overall survival (OS) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
OS is defined as time interval from recruitment to all-caused death or censoring.
safety as measured by the rate of adverse events (AEs), laboratory abnormalities, dose adjustment, discontinuation of administration, early discontinuation of the study drug, and delay to surgery.
Adverse events (AEs) of neoadjuvant therapy will be graded and documented according to NCI-CTCAE v4.0 from the beginning of treatment to 1 months after the last date of treatment. Documentary will include severity, lasting period and occurrence time. Main AEs include vomiting, diarrhea, anemia, leukopenia, thrombocytopenia, hand-foot syndrome, epidermal capillary hyperplasia, immune related adverse events (including pneumonia, interstitial lung disease, AST/ALT elevations, rash, diarrhea, hypothyroidism and hyperthyroidism) and hyper-progressive tumor.
AEs of surgery refer to complications which happen during or in 30 days after operation. Severe complications after operation such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, incision complications (infection, bleeding, rupture) will be observed and classified by Clavien-Dindo grading.
R0 resection rate
To evaluate the R0 resection rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Full Information
NCT ID
NCT03878472
First Posted
March 14, 2019
Last Updated
March 30, 2022
Sponsor
Qilu Hospital of Shandong University
1. Study Identification
Unique Protocol Identification Number
NCT03878472
Brief Title
Neoadjuvant Immunotherapy for Resectable Gastric Cancer
Official Title
A Phase II Clinical Study of Neoadjuvant Therapy for Resectable Locally Advanced Gastric Cancer With PD-1 Antibody or in Combination With Apatinib ± S1±Oxaliplatin
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2019 (Actual)
Primary Completion Date
May 1, 2022 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Qilu Hospital of Shandong University
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
Target population: patients with resectable locally advanced gastric cancer (cT3-4bN+M0).
Primary objective:
(1) To evaluate the pathological remission rate (PRR) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
(2) To evaluate the relationship between tumor pathological remission and biomarkers related to immunotherapy.
3. Secondary objectives:
To evaluate the imaging objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of PD-1 antibody alone or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant therapy for locally advanced gastric cancer.
To evaluate the safety of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Trial design: This is a monocenter, open, single arm, phase II study to evaluate the efficacy and safety of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant treatment of resectable locally advanced gastric cancer.
Detailed Description
Several important clinical trials including MAGIC, FLOT4, POET, RTOG 9904 and TOPGEAR have identified the efficacy and safety of neoadjuvant treatment in treating locally advanced GEJ cancer or gastric cancer.
patients with resectable locally advanced gastric cancer will receive neoadjuvant treatment of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin.
The investigators will shut down the study in advance, if situations below happens: 1) 1 treatment related death, >3 disease progression or >2 hyper-progressive disease happen during the first stage; 2) 2 treatment related death, >6 disease progression or >4 hyper-progressive disease happen during the whole study.
Patients with abnormal autoimmune status, unfavorable body function, factors impeding drug taking, absorption and metabolism will be excluded. Study participants with disease progression or severe/ intolerant toxicity during treatment will withdraw the study.
Hyper-progressive disease is defined as 1) progression 2) more than doubled growth rate 3) tumor volume increase >50% in 2 months after initialing the treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Neoadjuvant immunotherapy with PD-1
Arm Type
Experimental
Arm Title
Neoadjuvant immunotherapy with PD-1+apatinib
Arm Type
Experimental
Arm Title
Neoadjuvant immunotherapy with PD-1+apatinib+S1
Arm Type
Experimental
Arm Title
Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SHR1210
Intervention Description
The patients will receive at least two cycles of SHR-1210 (200 mg, invdrip d1) every two weeks and be accessed for operational suitability every two cycles.
Intervention Type
Drug
Intervention Name(s)
Apatinib
Intervention Description
The patients will received apatinib (250mg po qd) until 10 ± 2 days before surgery.
Intervention Type
Drug
Intervention Name(s)
S1
Intervention Description
The patients will received S1 (50 mg/m2, po, bid, d1-d10) every two weeks and be accessed for operational suitability every two cycles.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
The patients will receive at least two cycles of oxaliplatin (85 mg/m2 d1) every two weeks and be accessed for operational suitability every two cycles.
Primary Outcome Measure Information:
Title
Pathological remission rate (PRR) rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Description
The pathological response was calculated according to the proportion of residual viable tumor cells in the tumor bed. Complete pathological response (CPR) was defined as no residue tumor cells. Major pathological response (MPR) was defined as less than 10% residue tumor cells.
Time Frame
5 months after the last subject participating in
Title
Immunotherapy-related biomarkers
Description
To evaluate the relationship between tumor pathological remission and immunotherapy related biomarkers, including tumor genome, tumor microenvironment and host immune system response biomarkers.
Time Frame
5 months after the last subject participating in
Secondary Outcome Measure Information:
Title
objective response rate (ORR) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Description
rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1. However, responses do not require confirmation according to RECIST v 1.1. ORR was evaluated by chest, abdominal & pelvic CT/MRI.
Time Frame
Time Frame: 36 months after the last subject participating in
Title
progression free survival (PFS)of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Description
PFS is defined as time interval from recruitment to tumor progression. Tumor progression is defined as below: 1) tumor re-occurrence, 2) death, 3) censoring, and 4) beginning to use any other anti-tumor medicines.
Time Frame
Time Frame: 36 months after the last subject participating in
Title
overall survival (OS) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Description
OS is defined as time interval from recruitment to all-caused death or censoring.
Time Frame
Time Frame: 36 months after the last subject participating in
Title
safety as measured by the rate of adverse events (AEs), laboratory abnormalities, dose adjustment, discontinuation of administration, early discontinuation of the study drug, and delay to surgery.
Description
Adverse events (AEs) of neoadjuvant therapy will be graded and documented according to NCI-CTCAE v4.0 from the beginning of treatment to 1 months after the last date of treatment. Documentary will include severity, lasting period and occurrence time. Main AEs include vomiting, diarrhea, anemia, leukopenia, thrombocytopenia, hand-foot syndrome, epidermal capillary hyperplasia, immune related adverse events (including pneumonia, interstitial lung disease, AST/ALT elevations, rash, diarrhea, hypothyroidism and hyperthyroidism) and hyper-progressive tumor.
AEs of surgery refer to complications which happen during or in 30 days after operation. Severe complications after operation such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, incision complications (infection, bleeding, rupture) will be observed and classified by Clavien-Dindo grading.
Time Frame
Time Frame: 1 month after the last date of treatment
Title
R0 resection rate
Description
To evaluate the R0 resection rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.
Time Frame
5 months after the last subject participating in
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18-70 years old, both genders, histologically documented gastric cancer.
Newly diagnosed locally advanced, potentially resectable disease without any prior antitumor treatment
clinically diagnosed stage T3-4bN+M0 according to ultrasound endoscopy or enhanced CT/MRI scan.
Eligible and reasonably suitable for potentially curative resection
Written (signed) informed consent.
Pathological tissue available
ECOG: 0-1.
Adequate organ function.
Willingness to provide blood and tissue samples for research purposes.
Good compliance with the study procedures, including lab and auxiliary examination and treatment.
Female patients should not be pregnant or breast feeding.
Agree to take contraception measures during treatment and in 120 days after last dose of SHR-1210.
Life expectancy of at least 6 months.
Exclusion Criteria:
Patients with distant metastasis.
History of chemotherapy, radiation, immunotherapy, or radical resection of gastric cancer.
patients with active autoimmune disease or history of refractory autoimmune disease.
patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ.
uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
perforation / fistula of GI tract in 6 months before recruitment.
pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis, pulmonary fibrosis, acute pulmonary disease.
uncontrollable systemic diseases, including diabetes, hypertension etc.
severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB or HIV, etc.
patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV RNA.
patients with any cardiovascular risk factors below: （1）cardiac chest pain occurring in 28 days before recruitment, defined as moderate pain that limits daily activity.
（2）pulmonary embolism with symptoms occurring in 28 days before recruitment. （3）acute myocardial infarction occurring in 6 months before recruitment. （4）any history of heart failure reaching grade 3/4 of NYHA in 6 months before recruitment.
（5）ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, or accompanied by supraventricular tachyarrhythmias requiring medical treatment.
（6）cerebrovascular accident within 6 months before recruitment. 14. patients with peripheral neuropathy NCI CTC AE grade 1, except those with only deep tendon reflex disappearing.
15. moderate or severe renal injury [creatinine clearance rate≤50 ml/min (according to Cockcroft & Gault equation)], or Scr>ULN.
16. dipyrimidine dehydrogenase (DPD) deficiency. 17. allergic to any drug in this study. 18. history of allogeneic stem cell transplantation or organ transplantation. 19. use of steroids (dosage>10mg/d prednisone) or other systemic immune suppressive therapy in 14 days before recruitment, except patients treated with regimens below: a. steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local application with little systemic absorption; c. short -term (≤ 7 days) steroids for preventing allergy or vomiting.
20. vaccinated with live vaccine in 4 weeks before recruitment. 21. for patients with uncontrolled epilepsy, CNS diseases or history of mental disorder, researchers should evaluate whether their diseases will impede their signing of informed consent or compliance of treatment.
22. existing of potential situation which will impede drug administration or affect toxicity analysis or alcohol/ drug abuse.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lian Liu, Doctor
Phone
+8613705319315
Email
tounao@126.com
Facility Information:
Facility Name
Qilu hospital of Shandong univertisy
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250012
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lian Liu, doctor
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Neoadjuvant Immunotherapy for Resectable Gastric Cancer
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