Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

— PALACE-2  

Official title:

Multicenter Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophageus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04435197
• Other study ID #: RTS-010
• Status: Recruiting
• Phase: Phase 2
• Start date: August 11, 2020
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: Ruijin Hospital
• Contact: Hecheng Li, MD,PHD
• Phone: 00862164370045
• Email: lihecheng2000[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable esophageal squamous cell carcinoma (ESCC) ,20 patients enrolled in Phase Ib PALACE-1(NCT03792347).The results showed that preoperative pembrolizumab with concurrent chemoradiotherapy was safe, did not delay surgery and induced a pCR in 55.6% of resected tumors. In this multicentre prospective study(PALACE-2),the investigators will evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Description:

For locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy followed by surgery has been recommended as the optimal therapeutic strategy.Patients who achieved pathologic complete response(pCR) after receiving neoadjuvant therapy were more likely to have better survival. And the pCR rates was 43.2% reported in NEOCRTEC5010 trial, 49% with ESCC in the CROSS trial and 33.3% in FFCD 990130.

In Phase Ib PALACE-1(NCT03792347), the investigators firstly present that preoperative pembrolizumab combined with chemoradiotherapy followed by surgery is safe.All 20 patients have received PPCT successfully, except 1 patient who missed the last dose of chemotherapy due to leukopenia. Grade 3 and higher adverse events (AEs) were observed in 13 patients (13/20, 65%), and 1 patient had a grade 5 AE. The most frequent grade 3 AE was lymphopenia (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR rate was 55.6% (10/18).

This study (PALACE-2) will evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma in multicentres.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 143
• Est. completion date: December 2025
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:

1. Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma.

2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

3. Patients approve and sign the informed consent

Exclusion Criteria:

1. Patients with active autoimmune disease or history of autoimmune disease.

2. Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications.

3. Subjects with a history of symptomatic interstitial lung disease.

4. History of allergy to study drug components.

5. Women must not be pregnant or breast-feeding.

6. Men with female partners (WOCBP) that are not willing to use contraception.

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

8. 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Pembrolizumab Injection
Pre-operative Pembrolizumab+chemoradiotherapy

Locations

Country	Name	City	State
China	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Ruijin Hospital, Shanghai JiaoTong University School of Medicine	Shanghai	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
Ruijin Hospital	Fujian Medical University Union Hospital, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Nanchang University, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response	Pathologic complete response was defined as pT0N0M0	1 month after resection
Secondary	3-year disease free survival	Percentage of Participants With 3-Year disease-Free Survival (DFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Disease free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.	3 years after resection
Secondary	Overall Survival (OS)	OS is defined as the time from enrollment to death due to any cause	5 years