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Combination of Toripalimab and Chemoradiotherapy in Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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).

Condition or disease Intervention/treatment Phase
Unresectable Esophageal Cancer Drug: Toripalimab Drug: Paclitaxel/Cisplatin Radiation: Intensity-modulated radiotherapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Combination of Toripalimab and Definitive Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
Actual Study Start Date : June 25, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. 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

  3. 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

  4. 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


Other Outcome Measures:
  1. 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

  2. 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



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04005170


Contacts
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Contact: Mian XI, MD 86-20-87343385 ximian@sysucc.org.cn

Locations
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China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guanzhou, Guangdong, China, 510060
Contact: Mian Xi, MD    +86-20-87343385    ximian@sysucc.org.cn   
Sponsors and Collaborators
Mian XI
Publications:
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Responsible Party: Mian XI, Associate professor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04005170    
Other Study ID Numbers: TORIDEFEC
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: July 5, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mian XI, Sun Yat-sen University:
Esophageal squamous cell carcinoma
Definitive chemoradiotherapy
Toripalimab
Clinical complete response
Additional relevant MeSH terms:
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Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Paclitaxel
Cisplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action