Pembrolizumab Plus Paclitaxel, Cisplatin Followed by Surgery for Locally Advanced ESCC (KEYSTONE-001)

Phase 2

Active, not recruiting

• Conditions: Stage III; Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Pembrolizumab Injection [Keytruda]

• Registration Number: NCT04389177
• 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 paclitaxel, cisplatin followed by Da Vinci robot radical surgery for locally advanced esophageal squamous cell carcinoma.

Detailed Description

The Preoperative 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 paclitaxel, cisplatin followed by Da Vinci robot radical surgery for locally advanced (stage III) esophageal squamous cell cancer. The purpose of this study is to observe and evaluate the efficacy and safety.

Study Timeline

• Study First Submitted: 2020-05-12
• Study First Submitted QC: 2020-05-12
• Study First Posted: 2020-05-15
• Study Start: 2020-07-08
• Primary Completion: 2022-02-17
• Status Verified: 2022-04
• Last Update Submitted: 2023-04-06
• Last Update Posted: 2023-04-10
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Histologically confirmed esophageal squamous cell carcinoma;
2. Potentially resectable cT3N1M0，cT1-3N2M0(stage III)(AJCC 8 TNM classification);
3. Have a performance status of 0 or 1 on the ECOG Performance Scale;
4. Age 18-70 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 esophageal cancer;
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

Group	Intervention	Description
Pembrolizumab+ Paclitaxel+Cisplatin	Pembrolizumab Injection [Keytruda]	Pembrolizumab 200mg D1; Paclitaxel 135mg/m2 D2; Cisplatin 20mg/m2 D2-D4; repeated every 3 weeks

Primary Outcome Measures

Name	Time	Method
Major pathologic response	3 months	Viable tumor comprised ≤ 10% of resected tumor specimens

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	3 months	Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions
Lymph node derating rate	At time of surgery	Lymph node derating rate
Disease-free survival (DFS)	24 months	DFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of relapse after radical resection at any site or death related to cancer (including toxicity), whichever occurred first.
Overall survival (OS)	24 months	Time from the enrollment to death of any cause
R0 resection rate	At time of surgery	R0 resection rate

Trial Locations

Locations (1)

Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China