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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03748134
Ethics application status
Date submitted
12/11/2018
Date registered
20/11/2018
Date last updated
2/02/2021

Titles & IDs
Public title
Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma
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
CIBI308A301
Universal Trial Number (UTN)
Trial acronym
ORIENT-15
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
Other interventions - Sintilimab
Treatment: Drugs - Placebo
Treatment: Drugs - Cisplatin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Fluorouracil

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

Active Comparator: Placebo + chemotherapy - Placebo in combination with investigator's choice of chemotherapy
TP regimen: Cisplatin + paclitaxel
or
CP regimen: Cisplatin + fluorourcil


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

Treatment: Drugs: Placebo
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

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
OS in overall population - 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)
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 - 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
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 - To compare the objective response rate between the two treatment arms in ITT 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 - To compare the progression-free survival between the two treatment arms in ITT population
Timepoint [2] 0 0
From date of randomization up to 28 months
Secondary outcome [3] 0 0
DCR in overall population - To compare the disease control rate between the two treatment arms in ITT population
Timepoint [3] 0 0
From date of randomization up to 28 months
Secondary outcome [4] 0 0
DoR in overall population - To compare the duration of response between the two treatment arms in ITT population
Timepoint [4] 0 0
From date of randomization up to 28 months
Secondary outcome [5] 0 0
ORR - PD-L1 positive - To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population
Timepoint [5] 0 0
From date of randomization up to 28 months
Secondary outcome [6] 0 0
DCR - PD-L1 positive - To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population
Timepoint [6] 0 0
From date of randomization up to 28 months
Secondary outcome [7] 0 0
DoR - PD-L1 positive - To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population
Timepoint [7] 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 within 12 months to randomization.

- 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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Brussels
Country [8] 0 0
Belgium
State/province [8] 0 0
Verviers
Country [9] 0 0
China
State/province [9] 0 0
Beijing
Country [10] 0 0
France
State/province [10] 0 0
Bettancourt La Ferree
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Caen
Country [13] 0 0
France
State/province [13] 0 0
Clermont Ferrand
Country [14] 0 0
France
State/province [14] 0 0
Dijon
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Poitiers
Country [19] 0 0
France
State/province [19] 0 0
Rouen
Country [20] 0 0
France
State/province [20] 0 0
VandÅ“uvre-lès-Nancy
Country [21] 0 0
Spain
State/province [21] 0 0
Cantabria
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Fuenlabrada
Country [24] 0 0
Spain
State/province [24] 0 0
Girona
Country [25] 0 0
Spain
State/province [25] 0 0
Lleida
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Spain
State/province [27] 0 0
Pamplona
Country [28] 0 0
Spain
State/province [28] 0 0
Sabadell
Country [29] 0 0
Spain
State/province [29] 0 0
Santiago De Compostela
Country [30] 0 0
Spain
State/province [30] 0 0
Sevilla
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia
Country [32] 0 0
Spain
State/province [32] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Innovent Biologics (Suzhou) Co. Ltd.
Address
Country

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.
Trial website
https://clinicaltrials.gov/show/NCT03748134
Trial related presentations / publications
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
Agnes Sun
Address 0 0
Country 0 0
Phone 0 0
+86 21 31820291
Fax 0 0
Email 0 0
xiaolei.sun@innoventbio.com
Contact person for scientific queries

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