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Completed

NCT Number: NCT03748134

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

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

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Key information

Conditions

Esophageal Squamous Cell Carcinoma Carcinoma Carcinoma, Squamous Cell Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Squamous Cell

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Border Medical Oncology, East Albury, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sintilimab

Biological

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

Cisplatin

Drug

75mg/m^2 IV Q3W day 1

paclitaxel

Drug

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

Fluorouracil

Drug

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

Placebo

Drug

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

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Innovent Biologics (Suzhou) Co. Ltd.

Industry

Collaborators

  • Fortrea

Registry information

Official study 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)

Important dates

Study start
2018
Primary completion
2021
Study completion
2023
First posted
Nov 20, 2018
Registry last updated
Oct 24, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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