Clinical trial NCT04389177: Pembrolizumab Plus Paclitaxel, Cisplatin Followed by Surgery for Locally Advanced ESCC (KEYSTONE-001)
Official title: Efficacy and Safety of Pembrolizumab Plus Paclitaxel, Cisplatin Followed by Surgery in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (KEYSTONE-001)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Stage III
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2020-05-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Major pathologic response
timeFrame: 3 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 3 months
measure: Disease-free survival (DFS)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
measure: Lymph node derating rate
timeFrame: At time of surgery
measure: R0 resection rate
timeFrame: At time of surgery
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Xiaobin Shang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: 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.
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.