Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma

Neoadjuvant Chemotherapy Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04813523
• Other study ID #: TianjinCIH20210169
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2021
• Est. completion date: March 31, 2024

Study information

• Verified date: March 2021
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: Hongjing Jiang, MD, PhD
• Phone: 8618622221069
• Email: jianghongjing[@]tmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Esophagogastric Junction
• Neoadjuvant Chemotherapy
• Pembrolizumab

Intervention

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.

Locations

Country	Name	City	State
China	Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major pathologic response (MPR)	Viable tumor comprised = 10% of resected tumor specimens	one month after surgery
Secondary	Progression-free survival (PFS)	Time from the enrollment to disease relapse after complete resection or death from any cause	24 months
Secondary	Overall survival (OS)	Time from the enrollment to death of any cause	24 months
Secondary	Pathologic complete response (pCR)	No tumor residue of resected tumor specimens	one month after surgery