Adenocarcinoma of Esophagogastric Junction, Neoadjuvant Chemotherapy, Pembrolizumab
Conditions
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.
Interventions
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.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major pathologic response (MPR) | one month after surgery | Viable tumor comprised ≤ 10% of resected tumor specimens |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 24 months | Time from the enrollment to disease relapse after complete resection or death from any cause |
| Overall survival (OS) | 24 months | Time from the enrollment to death of any cause |
| Pathologic complete response (pCR) | one month after surgery | No tumor residue of resected tumor specimens |
Countries
China
Contacts
Primary ContactHongjing Jiang, MD, PhD
Backup ContactXiaofeng Duan, MD, PhD
Outcome results
None listed