Clinical trial NCT04435197: Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma
Official title: Multicenter Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophageus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Immunotherapy
Pathologic complete response
preoperative pembrolizumab with concurrent chemoradiotherapy
Disease-free Survival
Median overall survival
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Fujian Medical University Union Hospital
name: Zhejiang University
name: The First Affiliated Hospital of Anhui Medical University
name: The First Affiliated Hospital of Nanchang University
First posted: 2020-06-17
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathologic complete response
timeFrame: 1 month after resection
Secondary outcomes:
measure: 3-year disease free survival
timeFrame: 3 years after resection
measure: Overall Survival (OS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai JiaoTong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine
name: Hecheng Li, MD&PHD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.