Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma ( ORIENT-15 )
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ClinicalTrials.gov Identifier: NCT03748134 |
Recruitment Status :
Completed
First Posted : November 20, 2018
Last Update Posted : October 24, 2023
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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: Cisplatin Drug: Paclitaxel Drug: Fluorouracil Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual 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 |
Actual Primary Completion Date : | September 9, 2021 |
Actual Study Completion Date : | July 29, 2023 |
Arm | Intervention/treatment |
---|---|
Experimental: Randomized Part: 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: Randomised Part: Active Comparator: Placebo + chemotherapy
Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
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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 Drug: Placebo For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1 |
Experimental: Open-label part: Sintilimab+ chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
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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 |
- 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)
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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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 |
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.
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
Responsible Party: | Innovent Biologics (Suzhou) Co. Ltd. |
ClinicalTrials.gov Identifier: | NCT03748134 |
Other Study ID Numbers: |
CIBI308A301 2020-000533-40 ( Registry Identifier: EudraCT ) |
First Posted: | November 20, 2018 Key Record Dates |
Last Update Posted: | October 24, 2023 |
Last Verified: | October 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
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 |