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

NCT04389177 | Unknown Phase 2 DMC

• 1 other identifier: TianjinCIH2020101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Squamous Cell Carcinoma; Stage III

Outcome Measures

Primary Outcomes (1)

• Major pathologic response

  Viable tumor comprised ≤ 10% of resected tumor specimens

  3 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  3 months

• Disease-free survival (DFS)

  24 months

• Overall survival (OS)

  24 months

• Lymph node derating rate

  At time of surgery

• R0 resection rate

  At time of surgery

Study Arms (1)

Pembrolizumab+ Paclitaxel+Cisplatin

EXPERIMENTAL

Pembrolizumab 200mg D1; Paclitaxel 135mg/m2 D2; Cisplatin 20mg/m2 D2-D4; repeated every 3 weeks

Drug: Pembrolizumab Injection [Keytruda]

Interventions

Pembrolizumab Injection [Keytruda] DRUG

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.

Also known as: Paclitaxel, Cisplatin

Pembrolizumab+ Paclitaxel+Cisplatin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed esophageal squamous cell carcinoma;
• Potentially resectable cT3N1M0，cT1-3N2M0(stage III)(AJCC 8 TNM classification);
• Have a performance status of 0 or 1 on the ECOG Performance Scale;
• Age 18-70 years old, both men and women;
• Be willing and able to provide written informed consent/assent for the trial;
• Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
• 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;
• 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.

You may not qualify if:

• Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer;
• Ineligibility or contraindication for esophagectomy;
• 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;
• 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);
• Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

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

Tianjin, Tianjin Municipality, 300060, China

Location

Related Publications (5)

• 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.

  PMID: 35280363 BACKGROUND

• 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.

  PMID: 35574384 BACKGROUND

• 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.

  PMID: 35433421 BACKGROUND

• 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.

  PMID: 35703028 BACKGROUND

• 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.

  PMID: 35158822 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

pembrolizumab; Paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Xiaobin Shang, MD,PhD

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 15, 2020
• Study Start: July 8, 2020
• Primary Completion: February 17, 2022
• Study Completion: December 31, 2024
• Last Updated: April 10, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)