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

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

Efficacy and Safety of Pembrolizumab Plus Paclitaxel, Cisplatin Followed by Surgery in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (KEYSTONE-001)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04389177
• Other study ID #: TianjinCIH2020101
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 8, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2022
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: n/a
• 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 paclitaxel, cisplatin followed by Da Vinci robot radical surgery for locally advanced esophageal squamous cell carcinoma.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: December 31, 2024
• Est. primary completion date: February 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Stage III

Intervention

Drug:
• Pembrolizumab Injection [Keytruda]
Neoadjuvant period:preoperative therapy with three cycles: Pembrolizumab 200mg D1; Paclitaxel 135mg/m2 D2; Cisplatin 20mg/m2 D2-D4; repeated every 3 weeks. Da Vinci robot radical surgery: Before surgery, head/abdomen/chest CT scan, type B ultrasonic, upper gastrointestinal contrast, endoscopic ultrasound (EUS), and gastroscopy with biopsy will be done. Surgery should be done within 4-6 weeks after last neoadjuvant treatment finished. Adjuvant period: Adjuvant treatment with pembrolizumab 200mg every 3 weeks (6 cycles) should be performed within 3-6 weeks after surgery if the surgical pathology result is not pCR. abdomen/chest CT scan will be performed every 3 month 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, 

References & Publications (5)

Kassab J, Saba L, Kassab R, Kourie HR. Tsunami of immunotherapies in the management of esophageal cancer. Immunotherapy. 2022 Aug;14(11):879-884. doi: 10.2217/imt-2022-0035. Epub 2022 Jun 15. — View Citation

Lv H, Tian Y, Li J, Huang C, Sun B, Gai C, Li Z, Tian Z. Neoadjuvant Sintilimab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma. Front Oncol. 2022 Apr 29;12:864533. doi: 10.3389/fonc.2022.864533. eCollection 2022. — View Citation

Shang X, Zhang W, Zhao G, Liang F, Zhang C, Yue J, Duan X, Ma Z, Chen C, Pang Q, Zhang W, Liu L, Ren X, Meng B, Zhang P, Ma Y, Zhang L, Li H, Kang X, Li Y, Jiang H. Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002). Front Oncol. 2022 Mar 31;12:831345. doi: 10.3389/fonc.2022.831345. eCollection 2022. — View Citation

Shang X, Zhao G, Liang F, Zhang C, Zhang W, Liu L, Li R, Duan X, Ma Z, Yue J, Chen C, Meng B, Ren X, Jiang H. Safety and effectiveness of pembrolizumab combined with paclitaxel and cisplatin as neoadjuvant therapy followed by surgery for locally advanced resectable (stage III) esophageal squamous cell carcinoma: a study protocol for a prospective, single-arm, single-center, open-label, phase-II trial (Keystone-001). Ann Transl Med. 2022 Feb;10(4):229. doi: 10.21037/atm-22-513. — View Citation

Teixeira Farinha H, Digklia A, Schizas D, Demartines N, Schafer M, Mantziari S. Immunotherapy for Esophageal Cancer: State-of-the Art in 2021. Cancers (Basel). 2022 Jan 22;14(3):554. doi: 10.3390/cancers14030554. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major pathologic response	Viable tumor comprised = 10% of resected tumor specimens	3 months
Secondary	Objective response rate (ORR)	Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions	3 months
Secondary	Disease-free survival (DFS)	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.	24 months
Secondary	Overall survival (OS)	Time from the enrollment to death of any cause	24 months
Secondary	Lymph node derating rate	Lymph node derating rate	At time of surgery
Secondary	R0 resection rate	R0 resection rate	At time of surgery

External Links

•   (Keystone-001): Interim analysis of a prospective, single-arm, single-center, phase II trial