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Combination of Toripalimab and Chemoradiotherapy in Esophageal Cancer

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ClinicalTrials.gov Identifier: NCT04005170
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : July 5, 2019
Sponsor:
Information provided by (Responsible Party):
Mian XI, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE June 26, 2019
First Posted Date  ICMJE July 2, 2019
Last Update Posted Date July 5, 2019
Actual Study Start Date  ICMJE June 25, 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2019)
clinical complete response rate [ Time Frame: 3 months after chemoradiotherapy (plus or minus 14 days) ]
Tumor response was evaluated 3 months after the completion of chemoradiotherapy based on CT or PET-CT scans, endoscopy with biopsies.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2019)
  • 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
  • 2-year progression-free survival [ Time Frame: From date of randomization 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 progression-free survival of the whole group
  • Duration of response [ Time Frame: From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 24 months ]
    Tumor response was evaluated every two months after chemoradiotherapy according to RECIST criteria
  • Incidence of treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: From the start of treatment to 2 year after the completion of treatment ]
    Toxicity of treatment was evaluated according to CTCAE 4.0
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 30, 2019)
  • The impact of PD-L1 expression on clinical response [ Time Frame: Baseline biopsies of primary tumor in esophagus ]
    To investigate the impact of programmed cell death-ligand 1 (PD-L1) expression on clinical response
  • The impact of IDO1 expression on clinical response [ Time Frame: Baseline biopsies of primary tumor in esophagus ]
    To investigate the impact of indoleamine 2,3-dioxygenase 1 (IDO1) expression on clinical response
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Combination of Toripalimab and Chemoradiotherapy in Esophageal Cancer
Official Title  ICMJE A Phase II Trial of Combination of Toripalimab and Definitive Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
Brief Summary Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. 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 definitive CRT in locally advanced esophageal squamous cell carcinoma (ESCC).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unresectable Esophageal Cancer
Intervention  ICMJE
  • Drug: Toripalimab
    Patients received toripalimab 240 mg on days 1 and 22 during radiotherapy followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year.
    Other Name: JS-001
  • Drug: Paclitaxel/Cisplatin
    Patients received 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 during radiotherapy.
    Other Name: TP
  • Radiation: Intensity-modulated radiotherapy
    All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.
    Other Name: IMRT
Study Arms  ICMJE Experimental: PD-1 group
All patients will receive standard fractionation radiation therapy (RT) scheme: 50.4 Gy in 28 fractions over 5-6 weeks, concurrently with 5 cycles of paclitaxel/cisplatin (paclitaxel 50mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and 2 cycles of toripalimab 240 mg on days 1, 22 followed by a maintenance phase of toripalimab IV 240 mg every 3 weeks for up to 1 year.
Interventions:
  • Drug: Toripalimab
  • Drug: Paclitaxel/Cisplatin
  • Radiation: Intensity-modulated radiotherapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 30, 2019)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed squamous cell carcinoma of the esophagus;
  2. Absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8);
  3. Not suitable for surgery (either for medical reasons or patient's choice);
  4. Age at diagnosis 18 to 70 years;
  5. No prior cancer therapy;
  6. Estimated life expectancy >6 months;
  7. Eastern Cooperative Oncology Group performance status ≤ 2
  8. No history of concomitant or previous malignancy;
  9. 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;
  10. 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. Patients with hematogenous metastasis disease at diagnosis;
  3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
  4. Patients who have a preexisting or coexisting bleeding disorder;
  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 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 hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mian XI, MD 86-20-87343385 ximian@sysucc.org.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04005170
Other Study ID Numbers  ICMJE TORIDEFEC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mian XI, Sun Yat-sen University
Study Sponsor  ICMJE Mian XI
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sun Yat-sen University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP