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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03748134




Registration number
NCT03748134
Ethics application status
Date submitted
12/11/2018
Date registered
20/11/2018
Date last updated
24/10/2023

Titles & IDs
Public title
Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma ( ORIENT-15 )
Scientific 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)
Secondary ID [1] 0 0
2020-000533-40
Secondary ID [2] 0 0
CIBI308A301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Esophageal Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Sintilimab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Fluorouracil
Treatment: Drugs - Placebo

Experimental: Randomized Part: Experimental: Sintilimab + chemotherapy - Sintilimab in combination with investigator's choice of chemotherapy

TP regimen: Cisplatin + paclitaxel

or

CP regimen: Cisplatin + fluorourcil

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

Experimental: Open-label part: Sintilimab+ chemotherapy - Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil


Treatment: Other: Sintilimab
For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight=60kg, 200mg IV Q3W day 1

Treatment: Drugs: Cisplatin
75mg/m\^2 IV Q3W day 1

Treatment: Drugs: 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

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

Treatment: Drugs: Placebo
For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight=60kg, 200mg IV Q3W day 1
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
OS in overall population
Timepoint [1] 0 0
From date of randomization until the date of death from any cause, assessed up to 40 months.
Primary outcome [2] 0 0
OS in PD-L1 positive population
Timepoint [2] 0 0
From date of randomization until the date of death from any cause, assessed up to 40 months.
Secondary outcome [1] 0 0
ORR in overall population
Timepoint [1] 0 0
From date of randomization up to 28 months.
Secondary outcome [2] 0 0
PFS in overall populationsubjects in ITT population
Timepoint [2] 0 0
From date of randomization up to 28 months
Secondary outcome [3] 0 0
DCR in overall population
Timepoint [3] 0 0
From date of randomization up to 28 months
Secondary outcome [4] 0 0
DoR in overall population
Timepoint [4] 0 0
From date of randomization up to 28 months
Secondary outcome [5] 0 0
ORR - PD-L1 positive
Timepoint [5] 0 0
From date of randomization up to 28 months
Secondary outcome [6] 0 0
DCR - PD-L1 positive
Timepoint [6] 0 0
From date of randomization up to 28 months
Secondary outcome [7] 0 0
DoR - PD-L1 positive
Timepoint [7] 0 0
From date of randomization up to 28 months
Secondary outcome [8] 0 0
PFS - PD-L1 positive
Timepoint [8] 0 0
From date of randomization up to 28 months

Eligibility
Key inclusion criteria
Key

* 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/07/2023
Sample size
Target
Accrual to date
Final
746
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Border Medical Oncology - East Albury
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2640 - East Albury
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
3079 - Heidelberg
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Oklahoma
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Belgium
State/province [7] 0 0
Corneel Heymanslaan 10
Country [8] 0 0
Belgium
State/province [8] 0 0
Herestraat 49
Country [9] 0 0
Belgium
State/province [9] 0 0
Hippocrate 10
Country [10] 0 0
Belgium
State/province [10] 0 0
Brussels
Country [11] 0 0
Belgium
State/province [11] 0 0
Verviers
Country [12] 0 0
China
State/province [12] 0 0
Beijing
Country [13] 0 0
France
State/province [13] 0 0
Bettancourt La Ferree
Country [14] 0 0
France
State/province [14] 0 0
Bordeaux
Country [15] 0 0
France
State/province [15] 0 0
Caen
Country [16] 0 0
France
State/province [16] 0 0
Clermont Ferrand
Country [17] 0 0
France
State/province [17] 0 0
Dijon
Country [18] 0 0
France
State/province [18] 0 0
Lille
Country [19] 0 0
France
State/province [19] 0 0
Marseille
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Poitiers
Country [22] 0 0
France
State/province [22] 0 0
Rouen
Country [23] 0 0
France
State/province [23] 0 0
Vandœuvre-lès-Nancy
Country [24] 0 0
Hungary
State/province [24] 0 0
Ráth György U. 7-9
Country [25] 0 0
Hungary
State/province [25] 0 0
Szent István U. 68
Country [26] 0 0
Spain
State/province [26] 0 0
Cantabria
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Fuenlabrada
Country [29] 0 0
Spain
State/province [29] 0 0
Girona
Country [30] 0 0
Spain
State/province [30] 0 0
Lleida
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Pamplona
Country [33] 0 0
Spain
State/province [33] 0 0
Sabadell
Country [34] 0 0
Spain
State/province [34] 0 0
Santiago De Compostela
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
Spain
State/province [36] 0 0
Valencia
Country [37] 0 0
Spain
State/province [37] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Innovent Biologics (Suzhou) Co. Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Fortrea
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT03748134
Trial related presentations / publications
Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, Wang B, Sun G, Ji Y, Cao G, Liu H, Cui T, Li N, Qiu W, Li G, Hou X, Luo H, Xue L, Zhang Y, Yue W, Liu Z, Wang X, Gao S, Pan Y, Galais MP, Zaanan A, Ma Z, Li H, Wang Y, Shen L; ORIENT-15 study group. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022 Apr 19;377:e068714. doi: 10.1136/bmj-2021-068714.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03748134