Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma (KEYSTONE-003)

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

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

Study Overview

• Status: Recruiting
• Conditions: Pembrolizumab; Neoadjuvant Chemotherapy; Adenocarcinoma of Esophagogastric Junction
• Intervention / Treatment: Drug: Pembrolizumab Injection [Keytruda]

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongjing Jiang, MD, PhD; Phone Number: 8618622221069; Email: jianghongjing@tmu.edu.cn
• Study Contact Backup: Name: Xiaofeng Duan, MD, PhD; Phone Number: 8613752437179; Email: xduan@tmu.edu.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital
      • Contact: Hongjing Jiang, MD,PhD; Phone Number: 8618622221069; Email: jianghongjing@tmu.edu.cn
      • Contact: Xiaofeng Duan, MD,PhD; Phone Number: 8613752437179; Email: xduan@tmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed AEG, Siewert type I or II;
2. Potentially resectable cT3-4a, any N, M0 (AJCC 8 TNM classification);
3. Have a performance status of 0 or 1 on the ECOG Performance Scale;
4. Age 18-75 years old, both men and women;
5. Be willing and able to provide written informed consent/assent for the trial;
6. Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
7. 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;
8. 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:

1. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for AEG;
2. Ineligibility or contraindication for esophagectomy;
3. 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;
4. 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);
5. Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.

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: Experimental: Pembrolizumab+Cisplatin+5-FU; 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.	Drug: Pembrolizumab Injection [Keytruda]; 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.; Other Names: 5-FU; Cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR)	Viable tumor comprised ≤ 10% of resected tumor specimens	one month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from the enrollment to death of any cause	24 months
Progression-free survival (PFS)	Time from the enrollment to disease relapse after complete resection or death from any cause	24 months
Pathologic complete response (pCR)	No tumor residue of resected tumor specimens	one month after surgery

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cisplatin; Pembrolizumab
• Other Study ID Numbers: TianjinCIH20210169

Drug and device information, study documents

• 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