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

Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer : a Phase Il Study

To evaluate efficacy and safety of Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) in resectable locally advanced gastric cancer.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: sintilimab+metronomic PLOF

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Huashan Hospital, Fudan University
    • Contact: Wanwei Zheng; Phone Number: +86 13816431448; Email: calebzww@yeah.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written Informed Consent Form
2. Male or female, age ≥ 18 years old
3. 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
4. No prior systemic therapy such as surgery, radiotherapy, or immunotherapy for the disease at hand
5. Consent to radical surgical treatment and no contraindications to surgery as determined by the surgeon
6. ECOG PS: 0-1 score
7. Expected survival > 6 months

8. 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;

9. Negative pregnancy test in women of childbearing age
10. Need to use contraception with an annual failure rate of less than 1% if there is a risk of conception

Exclusion Criteria:

1. Endoscopically show signs of active bleeding from the lesion
2. 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
3. Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or agents targeting CTLA-4, OX-40, CD137, etc.
4. Diagnosis of a malignant disease other than gastric cancer within 5 years prior to the first dose of therapy
5. Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose of the drug
6. Live vaccination within 30 days prior to the first administration of the drug
7. 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
8. Have received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment
9. Has not fully recovered from any intervention-induced toxicity and/or complications (excluding malaise or alopecia) prior to initiation of therapy
10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation
11. Known hypersensitivity to drugs used in this study
12. Known history of HIV infection
13. Untreated active hepatitis B
14. Active HCV infection
15. Pregnant or lactating women
16. The presence of any serious or uncontrolled systemic disease
17. Other factors that, in the judgment of the investigator, may affect the outcome of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: sintilimab+metronomic PLOF; 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)

Drug: sintilimab+metronomic PLOF; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 6 weeks after first dosing
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.	up to 6 weeks after first dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 to 6weeks after the end of treatment
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 to 6weeks after the end of treatment
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.	From enrollment to study completion, assessed up to 2 years
3-year overall-survival (OS) rate	Percentage of participants who survived from enrollment to the third year of follow-up.	From enrollment to study completion, assessed up to 3 years
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.	From enrollment to study completion, assessed up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of immune cells in peripheral blood	Peripheral blood will be analyzed for the number of immune cells after applying flow cytometry and mRNA sequencing.	From enrollment to study completion, assessed up to 3 years
Proportion of immune cells in peripheral blood	Peripheral blood will be analyzed for the proportion of immune cells after applying flow cytometry and mRNA sequencing.	From enrollment to study completion, assessed up to 3 years
Number of immune cells in tumor tissues	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.	From enrollment to study completion, assessed up to 3 years
Distribution of immune cells in tumor tissue	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.	From enrollment to study completion, assessed up to 3 years

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2023
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 28, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: KY2022-1018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No