Pembrolizumab in Post Radical Operation ESCC Patients With Lymph Node Positive ( KEYSTONE-004 )

Pembrolizumab for Adjuvant Treatment After R0 Resection of Thoracic ESCC Patients With Lymph Node Positive: A Single-arm, Open-label, PhaseⅡTrial

The purpose of this study is to observe and evaluate the efficacy and safety of postoperative adjuvant treatment of pembrolizumab in patients with thoracic esophageal squamous cell carcinoma （ESCC） who have not received neoadjuvant therapy before undergoing R0 resection, and have positive postoperative lymph nodes.

Study Overview

• Status: Recruiting
• Conditions: ESCC; Adjuvant Treatment; Lymph Node Positive; Pembrolizumab
• Intervention / Treatment: Drug: Pembrolizumab Injection [Keytruda]

Detailed Description

For patients with thoracic esophageal squamous cell carcinoma （ESCC） who have undergone R0 resection, have not received neoadjuvant therapy, and have positive postoperative lymph nodes, there is no international consensus on whether postoperative adjuvant therapy is required. The JCOG9204 study reported that for patients with ESCC with positive lymph nodes after R0 resection, postoperative adjuvant chemotherapy can improve the disease-free survival (DFS) of the ESCC patients. However, due to the adverse effects of chemotherapy, patients are often difficult to tolerate. We designed a single-arm, open-label, phase II trial of pembrolizumab for adjuvant treatment after R0 resection of thoracic ESCC Patients with lymph node positive. The purpose of this study is to observe and evaluate the efficacy and safety.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• 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: Chuangui Chen, MD, PhD; Phone Number: +8618622228653; Email: ccg209@163.com

Study Locations

• China
  • Tianjin, China, 300060
    • Recruiting
    • Tianjin Medical University Cancer Institute and Hospital
    • Contact: Hongjing Jiang, MD, PhD; Phone Number: +8618622221069; Email: jianghongjing@tmu.edu.cn
    • Contact: Chuangui Chen, MD, PhD; Phone Number: +8618622228653; Email: ccg209@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed ESCC;
2. Patients have not received neoadjuvant therapy.
3. Thoracic ESCC with R0 resection and positive postoperative lymph nodes;
4. Have a performance status of 0 or 1 on the ECOG Performance Scale;
5. Age 18-70 years old, both men and women;
6. Be willing and able to provide written informed consent/assent for the trial;
7. Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
8. 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;
9. Be willing to provide postoperative tissue specimens. After tumor recurrence, continue to be willing to provide tissue samples such as needle biopsy.

Exclusion Criteria:

1. Neoadjuvant therapy (radiotherapy, immunotherapy, or chemotherapy) for ESCC;
2. Non-R0 resection for ESCC;
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 pembrolizumab 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: Pembrolizumab for Postoperative Adjuvant Treatment of ESCC; Participants receive pembrolizumab 200 mg IV, Q3W, up to one year or disease progression or intolerance as postoperative adjuvant treatment of ESCC with pN+.	Drug: Pembrolizumab Injection [Keytruda]; Pembrolizumab 200 mg IV, Q3W, up to one year or disease progression or intolerance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from the enrollment to death of any cause	24 months
Disease-free survival (DFS)	Time from the enrollment to disease relapse after complete resection or death from any cause	24 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Study Director: Dingzhi Huang, MD, PhD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): April 30, 2022
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: E20210220A

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