Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Cancer

December 22, 2019 updated by: Jianhua Fu

A Phase II Trial of Combination of Toripalimab and Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

Neoadjuvant chemoradiotherapy (CRT) followed by surgery has become the standard treatment option for locally advanced esophageal cancer (EC). However, only 20% to 40% of EC patients can achieve pathologic complete response (pCR) after neoadjuvant CRT with favorable prognosis. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. The aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) combined with neoadjuvant CRT in locally advanced esophageal squamous cell carcinoma (ESCC).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

44

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 Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-Sen University Cancer Center
        • Contact:
        • Principal Investigator:
          • Jianhua Fu, MD

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. A histopathological diagnosis of resectable thoracic esophageal squamous cell carcinoma with a pre-treatment clinical stage of T1-4aN1-3M0 or T3-4aN0M0 according to the 8th edition of the UICC staging system;
  2. Patients who are anti-tumor treatment-naive;
  3. Estimated life expectancy >6 months
  4. Aged 18 to 70 years old of either gender
  5. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 100×109/L; c. hemoglobin ≥ 9g/dL; d. serum albumin ≥ 2.8g/dL; e. total bilirubin ≤ 1.5×ULN, ALT, AST and/or AKP ≤ 2.5×ULN; f. serum creatinine ≤ 1.5×ULN or creatinine clearance rate >60 mL/min;
  6. PS score of 0-1;
  7. Ability to understand the study and sign informed consent.

Exclusion Criteria:

  1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
  2. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
  3. Patients who have a preexisting or coexisting bleeding disorder;
  4. Other uncontrollable inoperable patients;
  5. Female patients who are pregnant or lactating;
  6. Inability to provide informed consent due to psychological, familial, social and other factors;
  7. Presence of CTC grade ≥ 3 peripheral neuropathy;
  8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
  9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
  10. Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
  11. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), 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;
  12. A history of interstitial lung disease or non-infectious pneumonia;
  13. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
  14. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

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: Toripalimab group
All patients will receive standard fractionation radiation therapy (RT) scheme: 44Gy in 20 fractions over 4 weeks, concurrently with 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 and 2 cycles of toripalimab 240 mg on days 1, 22. Esophagectomy is performed 6-8 weeks after CRT completion.
Drug: Toripalimab
Patients received toripalimab 240 mg IVDRIP on days 1 and 22 during neoadjuvant radiotherapy.
Other Names:
  • JS-001
Drug: Paclitaxel/cisplatin
Patients received 4 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22 during neoadjuvant radiotherapy.
Other Names:
  • TP
Radiation: Intensity-modulated radiotherapy
All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 44 Gy in 20 fractions over 4 weeks.
Other Names:
  • IMRT
Procedure: Esophagectomy
A transthoracic (Ivor-Lewis) esophagectomy is performed 6-8 weeks after CRT completion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic complete response rate
Time Frame: Three working days after surgery
The rate of pathologic complete response rate after neoadjuvant chemoradiotherapy.
Three working days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The 2-year overall survival of the whole group
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
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.
The 2-year disease-free survival of the whole group
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.
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time Frame: From the enrollment to the date of surgery
The neoadjuvant treatment-related adverse events
From the enrollment to the date of surgery
R0 resection rate
Time Frame: Three working days after surgery
The R0 resection rate of esophagectomy
Three working days after surgery
Perioperative complication rate
Time Frame: From date of surgery to 30 days later
The perioperative complication rate of esophagectomy
From date of surgery to 30 days later
Perioperative mortality
Time Frame: From date of surgery to 30 days later
The perioperative mortality of esophagectomy
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

Jianhua Fu

Investigators

  • Principal Investigator: Jianhua Fu, MD, Sun Yat-sen University

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)

June 25, 2019

Primary Completion (Anticipated)

June 30, 2020

Study Completion (Anticipated)

December 31, 2020

Study Registration Dates

First Submitted

June 26, 2019

First Submitted That Met QC Criteria

June 30, 2019

First Posted (Actual)

July 2, 2019

Study Record Updates

Last Update Posted (Actual)

December 26, 2019

Last Update Submitted That Met QC Criteria

December 22, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TORINEOEC

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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