Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus (PALACE-1)

November 20, 2023 updated by: Hecheng Li M.D., Ph.D

A Phase Ib Study of Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Esophageal cancer ranks the eighth most common cancer (the fifth most common cancer in China), while ESCC is the most common subtype in Asia (more than 90 % in china). Radical resection is thought to be the mainstay of esophageal cancer treatment and preoperative CRT is well applied in treating locally advanced esophageal cancer. In a multicohort, phase IB study, pembrolizumab was used in 23 unresectable esophageal cancer patients. In this clinical trial, the incidence of grade 3 treatment-related adverse events was 39 % without the appearance of grade 4 and higher-grade adverse event, while the overall response rate reached 30 %. The safety of immune checkpoint therapy for unresected esophageal cancers using nivolumab, a different PD-1 monoclonal antibody, has also been confirmed by high quality clinical trials.

This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200025
        • Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Arm 1:preoperative pembrolizumab with chemoradiotherapy group 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 6 weeks after completion of preoperative therapy described above.
Drug: Pembrolizumab
Arm1：Pre-operative Pembrolizumab+chemoradiotherapy
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
Time Frame: From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
The number of participants with grade 3 and higher-grade treatment-related adverse events. Adverse events were evaluated using CTCAE 4.0, grade 3 treatment-related adverse events and higher-grade adverse events were reported.
From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility (Number of Participants Who Finished Pembrolizumab With Chemoradiotherapy and Receive Surgery Within 4-6 Weeks After Preoperative Therapies)
Time Frame: From date of treatment allocation until surgery or definitive chemoradiotherapy was applied, whichever came first, assessed up to 5 months
The number of participants who finished pembrolizumab with chemoradiotherapy and receive surgery within 4-6 weeks after preoperative therapies.
From date of treatment allocation until surgery or definitive chemoradiotherapy was applied, whichever came first, assessed up to 5 months
Pathologic Complete Response
Time Frame: Two weeks after surgery
Pathologic complete response was defined as the lack of all signs of cancer in tissue samples removed during surgery after treatment with pembrolizumab and chemoradiotherapy.
Two weeks after surgery
Radiographic Response
Time Frame: From date of treatment allocation and during treatment period up to 3 months
To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1. Complete metabolic response (cMR), defined as a physiological distribution of FDG uptake on PET-CT with a SUVmax value of less than 4 with no nodal uptake.
From date of treatment allocation and during treatment period up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hecheng Li M.D., Ph.D

Investigators

  • Principal Investigator: Hecheng Li, MD PHD, Ruijin Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2019

Primary Completion (Actual)

March 17, 2020

Study Completion (Actual)

June 17, 2020

Study Registration Dates

First Submitted

December 28, 2018

First Submitted That Met QC Criteria

January 1, 2019

First Posted (Actual)

January 3, 2019

Study Record Updates

Last Update Posted (Estimated)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTS-007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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