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

• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04813523
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 36
• Patients Per Site Per Month: 0.8

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of Esophagogastric Junction; Neoadjuvant Chemotherapy; Pembrolizumab	Drug: Pembrolizumab Injection [Keytruda]	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Apr 1, 2021
• Anticipated Primary Completion Date: Mar 31, 2022
• Anticipated Study Completion Date: Mar 31, 2024

Arms and Interventions

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: Cisplatin 5-FU

Outcome Measures

Primary Outcome Measures

1. Major pathologic response (MPR) [one month after surgery]

   Viable tumor comprised ≤ 10% of resected tumor specimens

Secondary Outcome Measures

1. Progression-free survival (PFS) [24 months]

   Time from the enrollment to disease relapse after complete resection or death from any cause

2. Overall survival (OS) [24 months]

   Time from the enrollment to death of any cause

3. Pathologic complete response (pCR) [one month after surgery]

   No tumor residue of resected tumor specimens

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin	China	300060

Sponsors and Collaborators

• Tianjin Medical University Cancer Institute and Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tianjin Medical University Cancer Institute and Hospital
• ClinicalTrials.gov Identifier: NCT04813523
• Other Study ID Numbers: TianjinCIH20210169
• First Posted: Mar 24, 2021
• Last Update Posted: Mar 24, 2021
• Last Verified: Mar 1, 2021

• 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
• Additional relevant MeSH terms: Adenocarcinoma; Esophageal Neoplasms; Cisplatin; Pembrolizumab

Study Results

No Results Posted as of Mar 24, 2021