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

NCT ID: NCT04435197

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-11
• Study Completion Date: 2024-06-30

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.

Conditions

Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab Injection

Intervention Type: DRUG

Pre-operative Pembrolizumab+chemoradiotherapy

Interventions

Pembrolizumab Injection

Pre-operative Pembrolizumab+chemoradiotherapy

Intervention Type: DRUG

Other Intervention Names

Keytruda

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

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

Sponsors

Fujian Medical University Union Hospital

OTHER

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hecheng Li M.D., Ph.D

Chair of thoracic department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hecheng Li, MD&PHD

Role: PRINCIPAL_INVESTIGATOR

Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine

Locations

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 36003437 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33373868 (View on PubMed)

Other Identifiers

RTS-010

Identifier Type: -

Identifier Source: org_study_id