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Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma

Phase 2
Conditions
Adenocarcinoma of Esophagogastric Junction
Pembrolizumab
Neoadjuvant Chemotherapy
Interventions
Registration Number
NCT04813523
Lead Sponsor
Tianjin Medical University Cancer Institute and Hospital
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Experimental: Pembrolizumab+Cisplatin+5-FUPembrolizumab Injection [Keytruda]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.
Primary Outcome Measures
NameTimeMethod
Major pathologic response (MPR)one month after surgery

Viable tumor comprised ≤ 10% of resected tumor specimens

Secondary Outcome Measures
NameTimeMethod
Overall survival (OS)24 months

Time from the enrollment to death of any cause

Progression-free survival (PFS)24 months

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

Pathologic complete response (pCR)one month after surgery

No tumor residue of resected tumor specimens

Trial Locations

Locations (1)

Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital

🇨🇳

Tianjin, Tianjin, China

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