Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Locally Advanced Esophageal Cancer

June 24, 2020 updated by: RenJi Hospital

A Phase II Prospective, Open-label Clinical Trial of Neoadjuvant Chemoradiotherapy Combined With Perioperative Toripalimab in Patients With Locally Advanced Esophageal Squamous Cell Cancer

Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal squamous cell cancer (ESCC). However, only 20% to 40% of patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis and about 10% of patients have disease progression after chemoradiotherapy. How to improve the the efficacy of neoadjuvant therapy is an important clinical problem to be solved.

Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC especially in ESCC. In Keynote181 study, for patients with metastatic esophageal squamous cell carcinoma, regardless of PD-L1 expression, pembrolizumab significantly improved overall survival compared with chemotherapy. However, the efficacy and safety of immunotherapy therapy in surgery-based multidisciplinary treatment of local advanced esophageal cancer still need a lot of clinical studies to further confirm.

The aim of this study was to evaluate the efficacy and safety of the neoadjuvant chemoradiotherapy combined with perioperative toripalimab in patients with locally advanced esophageal squamous cell cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • Recruiting
        • Renji Hospital
        • Contact:
        • Principal Investigator:
          • Xiumei Ma, Doctor

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged 18 to 75 years old of either gender
  • Patients with histopathological confirmed resectable thoracic esophageal squamous cell carcinoma who are anti-tumor treatment-naive;
  • Clinical stage of T1-4aN1-2M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system;
  • ECOG PS score of 0-1;
  • The indexes of hematology, biochemistry and organ function meet the following requirements: a. white blood cell count (WBC) ≥ 3.0×109/L；b. neutrophil count (ANC) ≥ 1.5×109/L; c. platelets ≥ 85×109/L; d. hemoglobin ≥ 9g/dL; e. total bilirubin ≤ 14.4µmol/L; f. ALT ≤ 75U/L; g. serum creatinine ≤ 104µmol/L and creatinine clearance rate >60 mL/min;
  • Women of childbearing age must undergo a pregnancy test within 7 days before enrolling in the treatment, and those who are negative can be enrolled. Patients of childbearing age and their sexual partners agree to use reliable methods of contraception before entering the study, during the study, and at least 180 days after the end of the study;
  • Ability to understand the study and sign informed consent.

Exclusion Criteria:

  • Patients with active infection within 2 weeks before the first use of the study drug or need to be treated with oral or intravenous antibiotics;
  • A history of interstitial lung disease or non-infectious pneumonia;
  • Patients whose clinician judges surgery as the first choice for the best treatment;
  • A history of autoimmune diseases or abnormal immune system ;
  • Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction。
  • Patients diagnosed with any other malignant tumor within 5 years before enrollment, except for malignant tumors with low risk of recurrence and risk of death, such as fully treated basal cell or squamous cell skin and carcinoma in situ of the cervix;
  • Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
  • A history of immunodeficiency，including a positive HIV test result or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
  • Women during pregnancy or lactation;
  • Other situations not suitable for enrollment.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Toripalimab Group
All patients will receive radiation therapy scheme: 41.4Gy in 23 fractions over 5 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 45mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22,29 and 2 cycles of toripalimab 240 mg every 3 weeks after chemoradiotherapy. Esophagectomy is performed 6-8 weeks after CRT completion and after operation patients received 4 cycles of toripalimab 240 mg every 3 weeks for adjuvant treatment.
Drug: Toripalimab
Patients received toripalimab 240mg every 3 weeks 1-7 days after neoadjuvant chemoradiotherapy for 2 cycles before operation and 28-42 days after operation for 4 cycles.
Other Names:
  • JS-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathological Response Rate (MPR)
Time Frame: From date of surgery to 14 days later
No more than 10% of tumor cells were found in neoadjuvant surgical specimens.
From date of surgery to 14 days later

Secondary Outcome Measures

Outcome Measure
Time Frame
2-year disease-free survival
Time Frame: From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
2-year overall survival
Time Frame: From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months
From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 24 months
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time Frame: 60 days after the end protocol treatment
60 days after the end protocol treatment
Perioperative complication rate
Time Frame: From date of surgery to 30 days later
From date of surgery to 30 days later

Collaborators and Investigators

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

Sponsor

RenJi Hospital

Investigators

  • Principal Investigator: Xiumei Ma, doctor, Renji Hospital

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 (ANTICIPATED)

July 1, 2020

Primary Completion (ANTICIPATED)

December 31, 2021

Study Completion (ANTICIPATED)

December 31, 2023

Study Registration Dates

First Submitted

June 16, 2020

First Submitted That Met QC Criteria

June 16, 2020

First Posted (ACTUAL)

June 18, 2020

Study Record Updates

Last Update Posted (ACTUAL)

June 26, 2020

Last Update Submitted That Met QC Criteria

June 24, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Renji-KY2019-174

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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