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Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma (ORIENT-15)

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ClinicalTrials.gov Identifier: NCT03748134
Recruitment Status : Recruiting
First Posted : November 20, 2018
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
Innovent Biologics (Suzhou) Co. Ltd.

Study Description
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Brief Summary:

This is a randomized, double-blind multi-center, phase III study comparing the efficacy and safety of sintilimab or placebo in combination with chemotherapy as first-line treatment in subjects with unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma.

After the interim analysis conducted by the iDMC, an open-label assignment of experimental arm therapy will continue in regions outside of China, in order to further evaluate the efficacy and safety of sintilimab in combination with chemotherapy in subjects representing the western population with advanced esophageal squamous cell carcinoma


Condition or disease Intervention/treatment Phase
Esophageal Squamous Cell Carcinoma Biological: Sintilimab Drug: Placebo Drug: Cisplatin Drug: Paclitaxel Drug: Fluorouracil Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 746 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-Blind, Randomized Phase 3 Clinical Trial Evaluating the Efficacy and Safety of Sintilimab vs. Placebo, in Combination With Chemotherapy, for First-Line Treatment of Unresectable, Locally Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma (ORIENT-15)
Actual Study Start Date : December 24, 2018
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Sintilimab + chemotherapy

Sintilimab in combination with investigator's choice of chemotherapy

TP regimen: Cisplatin + paclitaxel

or

CP regimen: Cisplatin + fluorourcil

 Biological: Sintilimab
For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1

Drug: Cisplatin
75mg/m^2 IV Q3W day 1

Drug: Paclitaxel
87.5 mg/m^2 IV Q3W day 1, day 8 for first cycle and 175mg/m^2 IV Q3W day 1 after first cycle

Drug: Fluorouracil
800 mg/m^2 IV continuous infusion over 24 hours daily on Days 1-5 Q3W
Active Comparator: Placebo + chemotherapy

Placebo in combination with investigator's choice of chemotherapy

TP regimen: Cisplatin + paclitaxel

or

CP regimen: Cisplatin + fluorourcil

 Drug: Placebo
For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1

Drug: Cisplatin
75mg/m^2 IV Q3W day 1

Drug: Paclitaxel
87.5 mg/m^2 IV Q3W day 1, day 8 for first cycle and 175mg/m^2 IV Q3W day 1 after first cycle

Drug: Fluorouracil
800 mg/m^2 IV continuous infusion over 24 hours daily on Days 1-5 Q3W


Outcome Measures
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Primary Outcome Measures :
  1. OS in overall population [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 40 months. ]
    To compare the overall survival of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC)

  2. OS in PD-L1 positive population [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 40 months. ]
    To compare the OS of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with PD-L1 positive, unresectable, locally advanced, recurrent or metastatic ESCC


Secondary Outcome Measures :
  1. ORR in overall population [ Time Frame: From date of randomization up to 28 months. ]
    To compare the objective response rate between the two treatment arms in ITT population

  2. PFS in overall populationsubjects in ITT population [ Time Frame: From date of randomization up to 28 months ]
    To compare the progression-free survival between the two treatment arms in ITT population

  3. DCR in overall population [ Time Frame: From date of randomization up to 28 months ]
    To compare the disease control rate between the two treatment arms in ITT population

  4. DoR in overall population [ Time Frame: From date of randomization up to 28 months ]
    To compare the duration of response between the two treatment arms in ITT population

  5. ORR - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
    To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population

  6. DCR - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
    To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population

  7. DoR - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
    To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population

  8. PFS - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
    To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic ESCC (excluding mixed adenosquamous carcinoma and other histological subtypes)
  • ECOG PS of 0 or 1
  • Subject must be unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery. For subjects who have received (neo)adjuvant or definitive chemotherapy/radiochemotherapy, time from the completion of last treatment to disease recurrence must be > 6 months Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results
  • Have at least one measurable lesion as per RECIST v1.1

Key exclusion Criteria:

  • ESCC with endoscopy-confirmed near-complete obstruction requiring interventional therapy
  • Post stent implantation in the esophagus or trachea with risk of perforation
  • Received systemic treatment for advanced or metastatic ESCC.
  • Received a cumulative dose of cisplatin ≥ 300 mg/m2 and the last cisplatin dose was within 12 months of randomization or the first dose of study treatment in the open-label phase.
  • High risk of hemorrhage or perforations due to tumor invasion in adjacent organs (aorta or trachea), or have fistula formation.
  • Hepatic metastasis > 50% of the total liver volume.
  • Received palliative therapy for a local lesion within 2 weeks prior to the first dose.
  • Received systemic treatment with Chinese traditional medicines with anti-cancer indications or immunomodulators (including thymosins, interferons, and interleukins) within 2 weeks prior to the first dose of study treatment.
  • Received systemic immunosuppressants within 2 weeks prior to randomization, excluding local use of glucocorticoids administered by nasal, inhaled, or other routes, and systemic glucocorticoids at physiological doses (no more than 10 mg/day of prednisone or equivalents), or glucocorticoids to prevent allergies to contrast media.
Contacts and Locations
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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): NCT03748134


Contacts
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Contact: Winnie Leung +86 21 31837200 winnie.leung@innoventbio.com
Contact: Peter Pan +86 21 31655781 xinchun.pan@innoventbio.com

Locations
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Sponsors and Collaborators
Innovent Biologics (Suzhou) Co. Ltd.
More Information
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Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
ClinicalTrials.gov Identifier: NCT03748134    
Other Study ID Numbers: CIBI308A301
First Posted: November 20, 2018    Key Record Dates
Last Update Posted: November 17, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Innovent Biologics (Suzhou) Co. Ltd.:
ESCC
Esophageal Cancer
Esophageal Neoplasms
Esophageal Neoplasms Malignant
Esophageal Squamous Cell Carcinoma
Neoplasms, Squamous Cell
Esophageal Diseases
Carcinoma, Squamous Cell
 Gastrointestinal Diseases
Paclitaxel
Cisplatin
Fluorouracil
Antineoplastic Agents
Anti-PD-1
Sintilimab
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
 Gastrointestinal Diseases
Paclitaxel
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs