Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma (KEYSTONE-003)
Primary Purpose
Adenocarcinoma of Esophagogastric Junction, Neoadjuvant Chemotherapy, Pembrolizumab
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Pembrolizumab Injection [Keytruda]
Sponsored by
About this trial
This is an interventional treatment trial for Adenocarcinoma of Esophagogastric Junction
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed AEG, Siewert type I or II;
- Potentially resectable cT3-4a, any N, M0 (AJCC 8 TNM classification);
- Have a performance status of 0 or 1 on the ECOG Performance Scale;
- Age 18-75 years old, both men and women;
- Be willing and able to provide written informed consent/assent for the trial;
- Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
Exclusion Criteria:
- Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for AEG;
- Ineligibility or contraindication for esophagectomy;
- 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 7 days prior to the first dose of study drug;
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs);
- Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.
Sites / Locations
- Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental: Pembrolizumab+Cisplatin+5-FU
Arm Description
Participants receive preoperative pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), cisplatin 80 mg/m^2 IV Q3W, and 5-FU 600 mg/m^2/day IV infusion on Days 1 to 5. There are 3 cycels of preoprative therapy and 3 cycles of postoperative therapy.
Outcomes
Primary Outcome Measures
Major pathologic response (MPR)
Viable tumor comprised ≤ 10% of resected tumor specimens
Secondary Outcome Measures
Progression-free survival (PFS)
Time from the enrollment to disease relapse after complete resection or death from any cause
Overall survival (OS)
Time from the enrollment to death of any cause
Pathologic complete response (pCR)
No tumor residue of resected tumor specimens
Full Information
NCT ID
NCT04813523
First Posted
March 22, 2021
Last Updated
March 22, 2021
Sponsor
Tianjin Medical University Cancer Institute and Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04813523
Brief Title
Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma
Acronym
KEYSTONE-003
Official Title
Efficacy and Safety of Pembrolizumab Plus Neoadjuvant Chemotherapy With Cisplatin and 5-Fluorouracill Followed by Surgery in Patients With Locally Advanced Adenocarcinoma of Esophagogastric Junction
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Anticipated)
Primary Completion Date
March 31, 2022 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
The purpose of this study is to observe and evaluate the efficacy and safety of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) followed Surgery for locally advanced adenocarcinoma of esophagogastric junction
Detailed Description
The neoadjuvant chemotherapy/chemoradiotherapy with surgery is the standard treatment in NCCN guideline. But many patients refused or abandon radiotherapy because of the intolerable adverse effects. We designed a single-arm, open-label, phase II trial of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) followed by radical surgery for locally advanced adenocarcinoma of esophagogastric junction. The purpose of this study is to observe and evaluate the efficacy and safety.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of Esophagogastric Junction, Neoadjuvant Chemotherapy, Pembrolizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Pembrolizumab+Cisplatin+5-FU
Arm Type
Experimental
Arm Description
Participants receive preoperative pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), cisplatin 80 mg/m^2 IV Q3W, and 5-FU 600 mg/m^2/day IV infusion on Days 1 to 5. There are 3 cycels of preoprative therapy and 3 cycles of postoperative therapy.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab Injection [Keytruda]
Other Intervention Name(s)
Cisplatin, 5-FU
Intervention Description
Neoadjuvant period: pembrolizumab 200mg IV, Q3W with three cycles. Adjuvant period: pembrolizumab 200 mg IV, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.
Primary Outcome Measure Information:
Title
Major pathologic response (MPR)
Description
Viable tumor comprised ≤ 10% of resected tumor specimens
Time Frame
one month after surgery
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Time from the enrollment to disease relapse after complete resection or death from any cause
Time Frame
24 months
Title
Overall survival (OS)
Description
Time from the enrollment to death of any cause
Time Frame
24 months
Title
Pathologic complete response (pCR)
Description
No tumor residue of resected tumor specimens
Time Frame
one month after surgery
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:
Histologically confirmed AEG, Siewert type I or II;
Potentially resectable cT3-4a, any N, M0 (AJCC 8 TNM classification);
Have a performance status of 0 or 1 on the ECOG Performance Scale;
Age 18-75 years old, both men and women;
Be willing and able to provide written informed consent/assent for the trial;
Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
Exclusion Criteria:
Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for AEG;
Ineligibility or contraindication for esophagectomy;
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 7 days prior to the first dose of study drug;
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs);
Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongjing Jiang, MD, PhD
Phone
8618622221069
Email
jianghongjing@tmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaofeng Duan, MD, PhD
Phone
8613752437179
Email
xduan@tmu.edu.cn
Facility Information:
Facility Name
Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongjing Jiang, MD,PhD
Phone
8618622221069
Email
jianghongjing@tmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Xiaofeng Duan, MD,PhD
Phone
8613752437179
Email
xduan@tmu.edu.cn
12. IPD Sharing Statement
Learn more about this trial
Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma
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