Pembrolizumab Plus Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Locally Advanced ESCC (KEYSTONE-002)

NCT ID: NCT04807673

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 342 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2028-05-31

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter.

Detailed Description

Preoperative chemoradiotherapy with radical surgery is the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC) in the NCCN guidelines. But many patients refused or abandon radiotherapy because of the intolerable adverse effects. The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter. The primary study hypothesis is that Event Free Survival (EFS) is superior with pembrolizumab plus neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy in participants with ESCC.

Conditions

Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m^2 IV on Day 2 Q3W, and cisplatin 80 mg/m^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year.

Surgery: McKeown esophagectomy

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

Neoadjuvant period: pembrolizumab 200mg IV D1, Q3W, and preoperative therapy with three cycles.

Adjuvant period: pembrolizumab 200 mg IV D1, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.

Paclitaxel

Intervention Type: DRUG

Neoadjuvant period: paclitaxel 135mg/m\^2 IV on Day 2 Q3W, and a total of three cycles.

Cisplatin

Intervention Type: DRUG

Neoadjuvant period: cisplatin 80 mg/m\^2 IV on Day 2 Q3W, and a total of three cycles.

neoadjuvant chemoradiotherapy+ Surgery (114)

neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m^2 on D1 and Cisplatin 25mg/m^2 D1, repeated every week. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment.

Surgery: McKeown esophagectomy

Group Type: EXPERIMENTAL

neoadjuvant chemoradiotherapy

Intervention Type: RADIATION

neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m\^2 on D1 and Cisplatin 25mg/m\^2 D1, repeated every week

Interventions

Pembrolizumab

Neoadjuvant period: pembrolizumab 200mg IV D1, Q3W, and preoperative therapy with three cycles.

Adjuvant period: pembrolizumab 200 mg IV D1, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.

Intervention Type: BIOLOGICAL

Paclitaxel

Neoadjuvant period: paclitaxel 135mg/m\^2 IV on Day 2 Q3W, and a total of three cycles.

Intervention Type: DRUG

Cisplatin

Neoadjuvant period: cisplatin 80 mg/m\^2 IV on Day 2 Q3W, and a total of three cycles.

Intervention Type: DRUG

neoadjuvant chemoradiotherapy

neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m\^2 on D1 and Cisplatin 25mg/m\^2 D1, repeated every week

Intervention Type: RADIATION

Other Intervention Names

Keytruda

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed esophageal squamous cell carcinoma;

2. R0 resectable thoracic esophageal cancer, cT1-3N1-2M0, cT2-3N0M0 (AJCC V8 TNM classification);

3. No suspicious metastatic lymph nodes on the clavicle;

4. Have a performance status of 0 or 1 on the ECOG Performance Scale;

5. Age 18-75 years old, both men and women;

6. Be willing and able to provide written informed consent/assent for the trial;

7. Demonstrate adequate organ function ;

8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours before 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;

9. Be willing to provide tissue, blood, and urine samples. Tissue should be 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) before initiation of treatment on Day 1.

10. Have not received systemic or local treatment for esophageal cancer in the past.

Exclusion Criteria

1. Ineligibility or contraindication for esophagectomy;

2. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer

3. Active autoimmune disease or history of autoimmune disease;

4. Requiring systemic treatment with either corticosteroids or other immunosuppressive medications;

5. Subjects with a history of symptomatic interstitial lung disease;

6. History of allergy to study drug components;

7. Women must not be pregnant or breast-feeding;

8. Patient has received prior chemotherapy, radiotherapy, target therapy ，and immune therapy for this malignancy or any other past malignancy;

9. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Shanghai Chest Hospital

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Hebei Medical University Fourth Hospital

OTHER

Sponsor Role: collaborator

Harbin Medical University

OTHER

Sponsor Role: collaborator

Liaoning Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Shanxi Province Cancer Hospital

OTHER

Sponsor Role: collaborator

Jining First People's Hospital

OTHER

Sponsor Role: collaborator

Weifang People's Hospital

OTHER

Sponsor Role: collaborator

Tianjin Medical University General Hospital

OTHER

Sponsor Role: collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hongjing Jiang, MD,PhD

Role: CONTACT

jianghongjing@tmu.edu.cn

18622221069

Xiaobin Shang, MD,PhD

Role: CONTACT

shangxiaobin@tmu.edu.cn

18622221071

Facility Contacts

Hongjing Jiang, MD,PhD

Role: primary

jianghongjing@tmu.edu.cn

18622221069

Xiaobin Shang, MD,PhD

Role: backup

shangxiaobin@tmu.edu.cn

18622221071

References

Al-Batran SE, Koch C. Neoadjuvant therapy for oesophageal cancer: refining the armamentarium. Lancet. 2024 Jul 6;404(10447):5-7. doi: 10.1016/S0140-6736(24)01084-5. Epub 2024 Jun 11. No abstract available.

Reference Type: DERIVED

PMID: 38876135 (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: DERIVED

PMID: 35433421 (View on PubMed)

Other Identifiers

TianjinCIH20210096

Identifier Type: -

Identifier Source: org_study_id