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Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer

Primary Purpose

Gastric Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
sintilimab+metronomic PLOF
Sponsored by
Huashan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer

Eligibility Criteria

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

Inclusion Criteria: Signed written Informed Consent Form Male or female, age ≥ 18 years old Histologically confirmed gastric adenocarcinoma, diagnosed as locally progressive according to the AJCC 8th ed, cTNM diagnosis of cT3-4aN1-3M0 and resectable lesion as assessed by the investigator No prior systemic therapy such as surgery, radiotherapy, or immunotherapy for the disease at hand Consent to radical surgical treatment and no contraindications to surgery as determined by the surgeon ECOG PS: 0-1 score Expected survival > 6 months Adequate organ function, must meet the following laboratory specifications: 8.1 Absolute neutrophil count (ANC) ≥ 1.0x10^9/L; 8.2 Platelets ≥ 80x10^9/L; 8.3 Hemoglobin > 7g/dL; 8.4 Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Total bilirubin > 1.5 x ULN but direct bilirubin ≤ ULN are allowed to be enrolled); 8.5 AST, ALT ≤ 2.5×ULN; 8.6 Blood creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 ml/min; 8.7 INR or PT ≤ 1.5 times ULN; 8.8 TSH within normal range (Enrollment allowed if baseline TSH is outside normal range but FT4 is within normal range); 8.9 Myocardial enzyme profile within normal range; Negative pregnancy test in women of childbearing age Need to use contraception with an annual failure rate of less than 1% if there is a risk of conception Exclusion Criteria: Endoscopically show signs of active bleeding from the lesion Current participation in an interventional clinical study or treatment with another investigational drug or use of an investigational device within 4 weeks prior to the first dose of study drug Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or agents targeting CTLA-4, OX-40, CD137, etc. Diagnosis of a malignant disease other than gastric cancer within 5 years prior to the first dose of therapy Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose of the drug Live vaccination within 30 days prior to the first administration of the drug Have received systemic systemic therapy with proprietary Chinese medicines with antitumor indications or immunomodulatory drugs within 2 weeks prior to the first administration of the drug Have received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment Has not fully recovered from any intervention-induced toxicity and/or complications (excluding malaise or alopecia) prior to initiation of therapy Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation Known hypersensitivity to drugs used in this study Known history of HIV infection Untreated active hepatitis B Active HCV infection Pregnant or lactating women The presence of any serious or uncontrolled systemic disease Other factors that, in the judgment of the investigator, may affect the outcome of the study

Sites / Locations

  • Huashan Hospital, Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sintilimab+metronomic PLOF

Arm Description

sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) followed by adjuvant sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) neoadjuvant chemotherapy (8 weeks) preceding surgery (3 weeks after completion of chemotherapy) followed by adjuvant chemotherapy (16 weeks, begin within 12 weeks after surgery)

Outcomes

Primary Outcome Measures

Percentage of participants with no residual surviving tumor cells in resection specimens and lymph nodes
Pathological complete response rate (pCR), defined as the proportion of participants with no residual viable tumor cells on microscopy and negative lymph nodes as a percentage of all participants. We will evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.
Percentage of participants with ≤10% tumor cell survival in resection specimens
Major pathologic response (MPR) rate, defined as the proportion of participants with ≤10% surviving tumor cells in the resection specimen as a percentage of all participants. We will evaluate major pathological response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.

Secondary Outcome Measures

Percentage of participants achieving complete remission (CR) and partial remission (PR) after treatment
Objective remission rate (ORR), the percentage of participants whose tumors shrink by a certain amount and remain there for a certain period of time, including complete remission (CR) and partial remission (PR). CR (Complete remission): Complete disappearance of the target lesion, with no new lesions produced, and lasting for more than 4 weeks. PR (Partial remission): the sum of the largest diameters of the target lesions is reduced by more than 30%, and lasts for more than 4 weeks.
Percentage of participants achieving remission (PR+CR) and lesion stabilization (SD) after treatment
Disease control rate (DCR) is the percentage of participants who achieve remission (PR+CR) and stabilization of lesions (SD) after the treatment. Stable disease (SD) means that the sum of the largest diameters of the tumor lesions has not shrunk to PR, or has not enlarged to PD.
2-year progression-free survival (PFS) rate
Percentage of participants who survived or were free of tumor progression from enrollment to the second year of follow-up.
3-year overall-survival (OS) rate
Percentage of participants who survived from enrollment to the third year of follow-up.
Number of participants with treatment-related adverse events as assessed by NCI-CTC
Toxicity deaths and early withdrawal from treatment due to toxic effects will be described. Toxicity assessment of adverse events and serious adverse events (SAEs) using the NCI-CTC.

Full Information

First Posted
September 12, 2023
Last Updated
September 22, 2023
Sponsor
Huashan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06054906
Brief Title
Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer
Official Title
Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer : A Phase Il Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huashan 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
To evaluate efficacy and safety of Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) in resectable locally advanced gastric cancer.
Detailed Description
This is a single-arm clinical study to enroll 50 patients with gastric cancer (cTNM diagnosis of cT3-4aN1-3M0). Each enrolled patient will be assigned a case number. Both this case number and the patient's initials will be entered on each page of the case report form. Enrolled patients receive a neoadjuvant regimen of POLF in combination with sindilizumab: preoperatively, they receive a POLF regimen (paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, and 5-fluorouracil 425 mg/m2) administered once weekly for a total of 6 doses, and in combination with sindilizumab 200 mg intravenously once every 3 weeks for a total of 2 doses. Upon completion of the evaluation, patients whose tumors were judged to be resectable underwent radical surgery and received six postoperative doses of the POLF regimen and two doses of Sindilizumab as adjuvant therapy. Postoperative imaging evaluations will be performed every three months until disease recurrence. Survival follow-up was performed every three months after disease recurrence. Patients will receive neoadjuvant therapy for 6 weeks preoperatively and adjuvant therapy for 6 weeks postoperatively unless intolerable toxicity occurs, the patient refuses to continue treatment, or treatment is delayed beyond 3 weeks. Patients will be under study observation during treatment and 30 days after treatment termination, and will receive long-term follow-up for 5 years postoperatively. Ultimately, pCR and MPR will be the primary study endpoints, and ORR, DCR, 2-year PFS rate, 3-year OS rate and safety will be the secondary study endpoints to evaluate the efficacy and safety of the neoadjuvant regimen of POLF combined with sindilizumab, as well as to explore the immune activation effect and mechanism of the regimen using peripheral blood and tumor tissue samples.

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
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
sintilimab+metronomic PLOF
Arm Type
Experimental
Arm Description
sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) followed by adjuvant sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) neoadjuvant chemotherapy (8 weeks) preceding surgery (3 weeks after completion of chemotherapy) followed by adjuvant chemotherapy (16 weeks, begin within 12 weeks after surgery)
Intervention Type
Drug
Intervention Name(s)
sintilimab+metronomic PLOF
Intervention Description
Drug: Sintilimab 200mg iv d1 Q3W, 2cycles Drug: Paclitaxel 60 mg/m2, d1, QW,6cycles Drug: Oxaliplatin 50 mg/m2, d1, QW, 6cycles Drug: 5-fluorouracil 425mg/m2 ,d1 ,QW, 6cycles
Primary Outcome Measure Information:
Title
Percentage of participants with no residual surviving tumor cells in resection specimens and lymph nodes
Description
Pathological complete response rate (pCR), defined as the proportion of participants with no residual viable tumor cells on microscopy and negative lymph nodes as a percentage of all participants. We will evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.
Time Frame
up to 6 weeks after first dosing
Title
Percentage of participants with ≤10% tumor cell survival in resection specimens
Description
Major pathologic response (MPR) rate, defined as the proportion of participants with ≤10% surviving tumor cells in the resection specimen as a percentage of all participants. We will evaluate major pathological response rate of primary tumor and locally metastatic lymph nodes after 6 weeks of neoadjuvant therapy.
Time Frame
up to 6 weeks after first dosing
Secondary Outcome Measure Information:
Title
Percentage of participants achieving complete remission (CR) and partial remission (PR) after treatment
Description
Objective remission rate (ORR), the percentage of participants whose tumors shrink by a certain amount and remain there for a certain period of time, including complete remission (CR) and partial remission (PR). CR (Complete remission): Complete disappearance of the target lesion, with no new lesions produced, and lasting for more than 4 weeks. PR (Partial remission): the sum of the largest diameters of the target lesions is reduced by more than 30%, and lasts for more than 4 weeks.
Time Frame
2 to 6weeks after the end of treatment
Title
Percentage of participants achieving remission (PR+CR) and lesion stabilization (SD) after treatment
Description
Disease control rate (DCR) is the percentage of participants who achieve remission (PR+CR) and stabilization of lesions (SD) after the treatment. Stable disease (SD) means that the sum of the largest diameters of the tumor lesions has not shrunk to PR, or has not enlarged to PD.
Time Frame
2 to 6weeks after the end of treatment
Title
2-year progression-free survival (PFS) rate
Description
Percentage of participants who survived or were free of tumor progression from enrollment to the second year of follow-up.
Time Frame
From enrollment to study completion, assessed up to 2 years
Title
3-year overall-survival (OS) rate
Description
Percentage of participants who survived from enrollment to the third year of follow-up.
Time Frame
From enrollment to study completion, assessed up to 3 years
Title
Number of participants with treatment-related adverse events as assessed by NCI-CTC
Description
Toxicity deaths and early withdrawal from treatment due to toxic effects will be described. Toxicity assessment of adverse events and serious adverse events (SAEs) using the NCI-CTC.
Time Frame
From enrollment to study completion, assessed up to 3 years
Other Pre-specified Outcome Measures:
Title
Number of immune cells in peripheral blood
Description
Peripheral blood will be analyzed for the number of immune cells after applying flow cytometry and mRNA sequencing.
Time Frame
From enrollment to study completion, assessed up to 3 years
Title
Proportion of immune cells in peripheral blood
Description
Peripheral blood will be analyzed for the proportion of immune cells after applying flow cytometry and mRNA sequencing.
Time Frame
From enrollment to study completion, assessed up to 3 years
Title
Number of immune cells in tumor tissues
Description
Apply mRNA sequencing, immunohistochemistry and immunofluorescence to analyze the number of immune cells in tumor tissues, including CTL, Treg, DC, TAM, MDSC, NK, NKT and so on.
Time Frame
From enrollment to study completion, assessed up to 3 years
Title
Distribution of immune cells in tumor tissue
Description
Apply mRNA sequencing, immunohistochemistry and immunofluorescence to analyze the distribution of immune cells in tumor tissues, including CTL, Treg, DC, TAM, MDSC, NK, NKT and so on.
Time Frame
From enrollment to study completion, assessed up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written Informed Consent Form Male or female, age ≥ 18 years old Histologically confirmed gastric adenocarcinoma, diagnosed as locally progressive according to the AJCC 8th ed, cTNM diagnosis of cT3-4aN1-3M0 and resectable lesion as assessed by the investigator No prior systemic therapy such as surgery, radiotherapy, or immunotherapy for the disease at hand Consent to radical surgical treatment and no contraindications to surgery as determined by the surgeon ECOG PS: 0-1 score Expected survival > 6 months Adequate organ function, must meet the following laboratory specifications: 8.1 Absolute neutrophil count (ANC) ≥ 1.0x10^9/L; 8.2 Platelets ≥ 80x10^9/L; 8.3 Hemoglobin > 7g/dL; 8.4 Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Total bilirubin > 1.5 x ULN but direct bilirubin ≤ ULN are allowed to be enrolled); 8.5 AST, ALT ≤ 2.5×ULN; 8.6 Blood creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 ml/min; 8.7 INR or PT ≤ 1.5 times ULN; 8.8 TSH within normal range (Enrollment allowed if baseline TSH is outside normal range but FT4 is within normal range); 8.9 Myocardial enzyme profile within normal range; Negative pregnancy test in women of childbearing age Need to use contraception with an annual failure rate of less than 1% if there is a risk of conception Exclusion Criteria: Endoscopically show signs of active bleeding from the lesion Current participation in an interventional clinical study or treatment with another investigational drug or use of an investigational device within 4 weeks prior to the first dose of study drug Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or agents targeting CTLA-4, OX-40, CD137, etc. Diagnosis of a malignant disease other than gastric cancer within 5 years prior to the first dose of therapy Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose of the drug Live vaccination within 30 days prior to the first administration of the drug Have received systemic systemic therapy with proprietary Chinese medicines with antitumor indications or immunomodulatory drugs within 2 weeks prior to the first administration of the drug Have received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment Has not fully recovered from any intervention-induced toxicity and/or complications (excluding malaise or alopecia) prior to initiation of therapy Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation Known hypersensitivity to drugs used in this study Known history of HIV infection Untreated active hepatitis B Active HCV infection Pregnant or lactating women The presence of any serious or uncontrolled systemic disease Other factors that, in the judgment of the investigator, may affect the outcome of the study
Facility Information:
Facility Name
Huashan Hospital, Fudan University
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wanwei Zheng
Phone
+86 13816431448
Email
calebzww@yeah.net

12. IPD Sharing Statement

Learn more about this trial

Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer

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