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

Sponsor

Ruijin Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04435197

Collaborator

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

143

Enrollment

Locations

Arm

57.7

Anticipated Duration (Months)

71.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Drug: Pembrolizumab Injection	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

143 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 11, 2020

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A 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.	Drug: Pembrolizumab Injection Pre-operative Pembrolizumab+chemoradiotherapy Other Names: Keytruda

Arm

Intervention/Treatment

Experimental: Arm A

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.

Drug: Pembrolizumab Injection

Pre-operative Pembrolizumab+chemoradiotherapy

Other Names:

Keytruda

Outcome Measures

Primary Outcome Measures

Pathologic complete response [1 month after resection]
Pathologic complete response was defined as pT0N0M0

Secondary Outcome Measures

3-year disease free survival [3 years after resection]
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) [5 years]
OS is defined as the time from enrollment to death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China	200025
2	Ruijin Hospital, Shanghai JiaoTong University School of Medicine	Shanghai	Shanghai	China	200025