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Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (PALACE-2)

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Pembrolizumab Injection

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring Immunotherapy, Pathologic complete response, preoperative pembrolizumab with concurrent chemoradiotherapy, Disease-free Survival, Median overall survival

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Patients approve and sign the informed consent

Exclusion Criteria:

Patients with active autoimmune disease or history of autoimmune disease.
Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications.
Subjects with a history of symptomatic interstitial lung disease.
History of allergy to study drug components.
Women must not be pregnant or breast-feeding.
Men with female partners (WOCBP) that are not willing to use contraception.
Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy.
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

Sites / Locations

Ruijin Hospital, Shanghai Jiao Tong University School of MedicineRecruiting
Ruijin Hospital, Shanghai JiaoTong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm A

Arm Description

Arm 1: A: Pembrolizumab 200mg(100mg if weight less than 50kg) IV on days 1 and 22 B: Carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. D: Ivor-Lewis or McKeown esophagectomy The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ，D will be performed if there is no contraindication.

Outcomes

Primary Outcome Measures

Pathologic complete response

Pathologic complete response was defined as pT0N0M0

Secondary Outcome Measures

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.

Overall Survival (OS)

OS is defined as the time from enrollment to death due to any cause

Full Information

NCT ID

NCT04435197

First Posted

June 14, 2020

Last Updated

April 20, 2023

Sponsor

Ruijin Hospital

Collaborators

Fujian Medical University Union Hospital, Zhejiang University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Nanchang University

1. Study Identification

Unique Protocol Identification Number

NCT04435197

Brief Title

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

Acronym

PALACE-2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 11, 2020 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ruijin Hospital

Collaborators

Fujian Medical University Union Hospital, Zhejiang University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Nanchang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Squamous Cell Carcinoma

Keywords

Immunotherapy, Pathologic complete response, preoperative pembrolizumab with concurrent chemoradiotherapy, Disease-free Survival, Median overall survival

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 1 and 22. Surgery will be performed within 4-6 weeks after completion of preoperative therapy.

Masking

None (Open Label)

Allocation

N/A

Enrollment

143 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab Injection

Other Intervention Name(s)

Keytruda

Intervention Description

Pre-operative Pembrolizumab+chemoradiotherapy

Primary Outcome Measure Information:

Title

Pathologic complete response

Description

Pathologic complete response was defined as pT0N0M0

Time Frame

1 month after resection

Secondary Outcome Measure Information:

Title

3-year disease free survival

Description

Time Frame

3 years after resection

Title

Overall Survival (OS)

Description

OS is defined as the time from enrollment to death due to any cause

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Patients approve and sign the informed consent Exclusion Criteria: Patients with active autoimmune disease or history of autoimmune disease. Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications. Subjects with a history of symptomatic interstitial lung disease. History of allergy to study drug components. Women must not be pregnant or breast-feeding. Men with female partners (WOCBP) that are not willing to use contraception. Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy. 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hecheng Li, MD,PHD

Phone

00862164370045

Ext

00862164370045

lihecheng2000@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Chengqiang Li, MD

Phone

00862164370045

whipple@yeah.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hecheng Li, MD&PHD

Organizational Affiliation

Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200025

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hecheng Li, MD,PHD

Phone

021-64370045

lihecheng2000@hotmail.com

First Name & Middle Initial & Last Name & Degree

Chengqiang Li, MD

Phone

13524282905

lcq12305@rjh.com.cn

First Name & Middle Initial & Last Name & Degree

Hecheng Li, MD,PHD

Facility Name

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200025

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chengqiang Li, MD

Phone

13524282905

Ext

666112

whipple@yeah.net

First Name & Middle Initial & Last Name & Degree

Yuyan Zheng, MD

Phone

00862164370045

Ext

666112

yuyanzheng@outlook.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

36003437

Citation

Zheng Y, Li C, Yu B, Zhao S, Li J, Chen X, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial design. JTCVS Open. 2021 Nov 10;9:293-299. doi: 10.1016/j.xjon.2021.11.003. eCollection 2022 Mar.

Results Reference

derived

PubMed Identifier

33373868

Citation

Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.

Results Reference

derived

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

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