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Tislelizumab in Combination With Pre-operative CRT Versus SOC for Locally Advanced G/GEJ Adenocarcinoma

Primary Purpose

Gastric Cancer, Gastroesophageal-junction Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
S-1
Oxaliplatin
Nab paclitaxel
Radiation
Sponsored by
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer

Eligibility Criteria

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

Inclusion Criteria: Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3~4aN+M0 or T4bNanyM0 （AJCC Version 8） Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 Has adequate organ function. Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater. Exclusion Criteria: Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy. Has an active infection requiring systemic therapy. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment. Has an active autoimmune disease that has required systemic treatment in past 2 years. Has a known history of human immunodeficiency virus (HIV) infection. Has a known history of Hepatitis B or known active Hepatitis C virus infection (HBsAg positive with HBV DNA≥500 IU/ml；HCV：HCV antigen positive with HCV copies >ULN). Has had an allogenic tissue/solid organ transplant. Has received a live vaccine within 30 days prior to the first dose of study treatment. Female participants who are breastfeeding.

Sites / Locations

  • Wuhan Tongji Hospital
  • Nanjing Drum Tower HospitalRecruiting
  • Shanxi Province Cancer Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Arm A: Tislelizumab + Chemoradiotherapy

Arm B: Chemoradiotherapy

Arm C: Chemotherapy

Arm Description

Neoadjuvant: Prior to surgery, participants receive 4 cycles of Tislelizumab 200 mg via intravenous (IV) infusion on C1D1, C2D1, C2D22, C3D1 PLUS radiotherapy (TOMO or VMAT) 45Gy/1.5f PLUS S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C2D1~C2D5, C2D8~C2D12, C2D15~C2D19, C2D22~C2D26, C2D29~C2D33, C3D1~D14 and oxaliplatin 130mg/m^2, IV, C1D1 and C3D1 OR S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C3D1~D14 and nab-paclitaxel, IV 100~120mg/m^2，IV，C1D1，C1D8，C2D1，C2D8，C2D16，C2D22，C3D1 and C3D8. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1, AND up to 16 cycles of Tislelizumab 200 mg via IV infusion on Day 1 Q3W.

Neoadjuvant: Prior to surgery, participants receive radiotherapy (TOMO or VMAT) 45Gy/1.5f PLUS S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C2D1~C2D5, C2D8~C2D12, C2D15~C2D19, C2D22~C2D26, C2D29~C2D33, C3D1~D14 and oxaliplatin 130mg/m^2, IV, C1D1 and C3D1 OR S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C3D1~D14 and nab-paclitaxel, IV 100~120mg/m^2，IV，C1D1，C1D8，C2D1，C2D8，C2D16，C2D22，C3D1 and C3D8. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1.

Neoadjuvant: S-1 initial dose depends on the body surface area, PO, bid, D1~D14，Q 3W for 6 cycles, and oxaliplatin 130mg/m^2, IV, D1 of each cycle for 6 cycles OR nab-paclitaxel, IV 100~120mg/m^2，IV，D1 and D8 for each cycle for 6 cycles. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1.

Outcomes

Primary Outcome Measures

Pathological Complete Response (pathCR) Rate
PathCR rate is defined as the percentage of participants having a pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.

Secondary Outcome Measures

Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.

Full Information

First Posted
December 26, 2022
Last Updated
April 17, 2023
Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
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1. Study Identification

Unique Protocol Identification Number
NCT05687357
Brief Title
Tislelizumab in Combination With Pre-operative CRT Versus SOC for Locally Advanced G/GEJ Adenocarcinoma
Official Title
Tislelizumab in Combination With Pre-operative Chemoradiotherapy Versus SOC for Patients With Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: a Multicenter, Randomized, Open-label, Phase IIB Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2023 (Actual)
Primary Completion Date
February 28, 2027 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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
The purpose of this study is to evaluate the efficacy of Tislelizumab in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The primary study hypotheses are that: Neoadjuvant and adjuvant Tislelizumab plus chemoradiotherapy, followed by adjuvant Tislelizumab and chemotherapy is superior to neoadjuvant chemoradiotherapy or chemotherapy, followed by adjuvant chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Gastroesophageal-junction Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Tislelizumab + Chemoradiotherapy
Arm Type
Experimental
Arm Description
Neoadjuvant: Prior to surgery, participants receive 4 cycles of Tislelizumab 200 mg via intravenous (IV) infusion on C1D1, C2D1, C2D22, C3D1 PLUS radiotherapy (TOMO or VMAT) 45Gy/1.5f PLUS S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C2D1~C2D5, C2D8~C2D12, C2D15~C2D19, C2D22~C2D26, C2D29~C2D33, C3D1~D14 and oxaliplatin 130mg/m^2, IV, C1D1 and C3D1 OR S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C3D1~D14 and nab-paclitaxel, IV 100~120mg/m^2，IV，C1D1，C1D8，C2D1，C2D8，C2D16，C2D22，C3D1 and C3D8. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1, AND up to 16 cycles of Tislelizumab 200 mg via IV infusion on Day 1 Q3W.
Arm Title
Arm B: Chemoradiotherapy
Arm Type
Active Comparator
Arm Description
Neoadjuvant: Prior to surgery, participants receive radiotherapy (TOMO or VMAT) 45Gy/1.5f PLUS S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C2D1~C2D5, C2D8~C2D12, C2D15~C2D19, C2D22~C2D26, C2D29~C2D33, C3D1~D14 and oxaliplatin 130mg/m^2, IV, C1D1 and C3D1 OR S-1 initial dose depends on the body surface area, PO, bid, C1D1~D14，C3D1~D14 and nab-paclitaxel, IV 100~120mg/m^2，IV，C1D1，C1D8，C2D1，C2D8，C2D16，C2D22，C3D1 and C3D8. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1.
Arm Title
Arm C: Chemotherapy
Arm Type
Active Comparator
Arm Description
Neoadjuvant: S-1 initial dose depends on the body surface area, PO, bid, D1~D14，Q 3W for 6 cycles, and oxaliplatin 130mg/m^2, IV, D1 of each cycle for 6 cycles OR nab-paclitaxel, IV 100~120mg/m^2，IV，D1 and D8 for each cycle for 6 cycles. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
S-1
Intervention Description
Oral tablets
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
IV infusion
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
TOMO/VMAT
Primary Outcome Measure Information:
Title
Pathological Complete Response (pathCR) Rate
Description
PathCR rate is defined as the percentage of participants having a pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.
Time Frame
Up to approximately 22 weeks
Secondary Outcome Measure Information:
Title
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Time Frame
Up to approximately 2 years
Title
Overall Survival (OS)
Description
OS is defined as the time from randomization to death due to any cause.
Time Frame
Up to approximately 2 years

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: Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3~4aN+M0 or T4bNanyM0 （AJCC Version 8） Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 Has adequate organ function. Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater. Exclusion Criteria: Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy. Has an active infection requiring systemic therapy. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment. Has an active autoimmune disease that has required systemic treatment in past 2 years. Has a known history of human immunodeficiency virus (HIV) infection. Has a known history of Hepatitis B or known active Hepatitis C virus infection (HBsAg positive with HBV DNA≥500 IU/ml；HCV：HCV antigen positive with HCV copies >ULN). Has had an allogenic tissue/solid organ transplant. Has received a live vaccine within 30 days prior to the first dose of study treatment. Female participants who are breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jia Wei, MD
Phone
0086-025-83304616
Email
jiawei99@nju.edu.cn
Facility Information:
Facility Name
Wuhan Tongji Hospital
City
Wuhan
State/Province
Hubei
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xianglin Yuan, MD
Facility Name
Nanjing Drum Tower Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jia Wei, MD
Phone
0086-025-83304616
Facility Name
Shanxi Province Cancer Hospital
City
Taiyuan
State/Province
Shanxi
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yusheng Wang, MD

12. IPD Sharing Statement

Learn more about this trial

Tislelizumab in Combination With Pre-operative CRT Versus SOC for Locally Advanced G/GEJ Adenocarcinoma

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