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

NCT ID: NCT04389177

Last Updated: 2023-04-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-08
• Study Completion Date: 2024-12-31

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.

Conditions

Esophageal Squamous Cell Carcinoma; Stage III

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab+ Paclitaxel+Cisplatin

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

Group Type: EXPERIMENTAL

Pembrolizumab Injection [Keytruda]

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Paclitaxel; Cisplatin

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiaobin Shang, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Tianjin Medical University Cancer Institute and Hospital

Locations

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

Tianjin, Tianjin Municipality, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 35280363 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35574384 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35433421 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35703028 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35158822 (View on PubMed)

Related Links

http://doi.org/10.1016/j.annonc.2021.10.218

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

Other Identifiers

TianjinCIH2020101

Identifier Type: -

Identifier Source: org_study_id