search
Back to results

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

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sintilimab
Cisplatin
Paclitaxel
Fluorouracil
Placebo
Sponsored by
Innovent Biologics (Suzhou) Co. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center
  • UC Irvine
  • Rocky Mountain Cancer Centers, LLP
  • IACT Health - John B. Amos Cancer center
  • Stephenson Cancer Center
  • Texas Oncology, P.A.
  • Northwest Cancer Specialists, P.C.
  • Border Medical Oncology
  • The Queen Elizabeth Hospital
  • Austin Hospital
  • Sir Charles Gairdner Hospital
  • St John of God Subiaco Hospital
  • University Hospital Gent
  • Universitair Ziekenhuis Leuven
  • Cliniques Universitaires Saint-Luc Av.
  • Institut Jules Bordet
  • Centre Hospitalier Regional de Verviers
  • Beijing Cancer Hospital
  • Hôpital Jean Minjoz
  • Institut Bergonié
  • Centre François Baclesse
  • CHU Estaing
  • CHU Estaing
  • Faculte de Medecine
  • Universite de Bourgogne - Faculte de Medecine - INSERM U866
  • Oscar Lambret Centre
  • CHU Hôpital de la Timone
  • Hôpital Européen Georges Pompidou
  • CHU de Poitiers
  • Hôpital Charles-Nicolle de Rouen
  • Institut de Cancérologie de Lorraine
  • Országos Onkológiai Intézet
  • Jósa András Oktatókórház
  • University Hospital Marqués de Valdecilla
  • Hospital del Mar
  • Hospital Universitario Vall d'Hebron
  • Hospital Universitario de Fuenlabrada
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Hospital Universitari Arnau de Vilanova de Lleida
  • Hospital Universitario Fundacion Jimenez Diaz
  • Hospital Universitario La Paz
  • Hospital Universitario Ramón y Cajal
  • Clínica Universidad de Navarra
  • Parc Taulí Sabadell Hospital Universitari
  • Complexo Hospitalario Universitario de Santiago
  • Hospital Universitario Virgen Macarena
  • Consorci Hospital General Universitari de València
  • Hospital Universitario Miguel Servet

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Randomized Part: Experimental: Sintilimab + chemotherapy

Randomised Part: Active Comparator: Placebo + chemotherapy

Open-label part: Sintilimab+ chemotherapy

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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)
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

Secondary Outcome Measures

ORR in overall population
To compare the objective response rate between the two treatment arms in ITT population
PFS in overall populationsubjects in ITT population
To compare the progression-free survival between the two treatment arms in ITT population
DCR in overall population
To compare the disease control rate between the two treatment arms in ITT population
DoR in overall population
To compare the duration of response between the two treatment arms in ITT population
ORR - PD-L1 positive
To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population
DCR - PD-L1 positive
To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population
DoR - PD-L1 positive
To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population
PFS - PD-L1 positive
To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population

Full Information

First Posted
November 12, 2018
Last Updated
October 22, 2023
Sponsor
Innovent Biologics (Suzhou) Co. Ltd.
Collaborators
Fortrea
search

1. Study Identification

Unique Protocol Identification Number
NCT03748134
Brief Title
Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma ( ORIENT-15 )
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
December 24, 2018 (Actual)
Primary Completion Date
September 9, 2021 (Actual)
Study Completion Date
July 29, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innovent Biologics (Suzhou) Co. Ltd.
Collaborators
Fortrea

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
746 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Randomized Part: Experimental: Sintilimab + chemotherapy
Arm Type
Experimental
Arm Description
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
Arm Title
Randomised Part: Active Comparator: Placebo + chemotherapy
Arm Type
Active Comparator
Arm Description
Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
Arm Title
Open-label part: Sintilimab+ chemotherapy
Arm Type
Experimental
Arm Description
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
Intervention Type
Biological
Intervention Name(s)
Sintilimab
Intervention Description
For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
75mg/m^2 IV Q3W day 1
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
800 mg/m^2 IV continuous infusion over 24 hours daily on Days 1-5 Q3W
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1
Primary Outcome Measure Information:
Title
OS in overall population
Description
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)
Time Frame
From date of randomization until the date of death from any cause, assessed up to 40 months.
Title
OS in PD-L1 positive population
Description
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
Time Frame
From date of randomization until the date of death from any cause, assessed up to 40 months.
Secondary Outcome Measure Information:
Title
ORR in overall population
Description
To compare the objective response rate between the two treatment arms in ITT population
Time Frame
From date of randomization up to 28 months.
Title
PFS in overall populationsubjects in ITT population
Description
To compare the progression-free survival between the two treatment arms in ITT population
Time Frame
From date of randomization up to 28 months
Title
DCR in overall population
Description
To compare the disease control rate between the two treatment arms in ITT population
Time Frame
From date of randomization up to 28 months
Title
DoR in overall population
Description
To compare the duration of response between the two treatment arms in ITT population
Time Frame
From date of randomization up to 28 months
Title
ORR - PD-L1 positive
Description
To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population
Time Frame
From date of randomization up to 28 months
Title
DCR - PD-L1 positive
Description
To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population
Time Frame
From date of randomization up to 28 months
Title
DoR - PD-L1 positive
Description
To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population
Time Frame
From date of randomization up to 28 months
Title
PFS - PD-L1 positive
Description
To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population
Time Frame
From date of randomization up to 28 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center
City
Anaheim
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
UC Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Rocky Mountain Cancer Centers, LLP
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
IACT Health - John B. Amos Cancer center
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Texas Oncology, P.A.
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States
Facility Name
Border Medical Oncology
City
East Albury
State/Province
New South Wales
ZIP/Postal Code
2640
Country
Australia
Facility Name
The Queen Elizabeth Hospital
City
Woodville South
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
Austin Hospital
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3079
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
St John of God Subiaco Hospital
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
University Hospital Gent
City
Gent
State/Province
Corneel Heymanslaan 10
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Universitair Ziekenhuis Leuven
City
Leuven
State/Province
Herestraat 49
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Cliniques Universitaires Saint-Luc Av.
City
Bruxelles
State/Province
Hippocrate 10
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Centre Hospitalier Regional de Verviers
City
Verviers
ZIP/Postal Code
4800
Country
Belgium
Facility Name
Beijing Cancer Hospital
City
Beijing
Country
China
Facility Name
Hôpital Jean Minjoz
City
Bettancourt La Ferree
ZIP/Postal Code
25000
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Centre François Baclesse
City
Caen
ZIP/Postal Code
14000
Country
France
Facility Name
CHU Estaing
City
Clermont Ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
CHU Estaing
City
Clermont Ferrand
ZIP/Postal Code
63100
Country
France
Facility Name
Faculte de Medecine
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Name
Universite de Bourgogne - Faculte de Medecine - INSERM U866
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Oscar Lambret Centre
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
CHU Hôpital de la Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Hôpital Charles-Nicolle de Rouen
City
Rouen
ZIP/Postal Code
76000
Country
France
Facility Name
Institut de Cancérologie de Lorraine
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54500
Country
France
Facility Name
Országos Onkológiai Intézet
City
Budapest
State/Province
Ráth György U. 7-9
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Jósa András Oktatókórház
City
Nyíregyháza
State/Province
Szent István U. 68
ZIP/Postal Code
4400
Country
Hungary
Facility Name
University Hospital Marqués de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08001
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario de Fuenlabrada
City
Fuenlabrada
ZIP/Postal Code
28942
Country
Spain
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Girona
Country
Spain
Facility Name
Hospital Universitari Arnau de Vilanova de Lleida
City
Lleida
ZIP/Postal Code
25198
Country
Spain
Facility Name
Hospital Universitario Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
280402
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Clínica Universidad de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Parc Taulí Sabadell Hospital Universitari
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Complexo Hospitalario Universitario de Santiago
City
Santiago De Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41003
Country
Spain
Facility Name
Consorci Hospital General Universitari de València
City
Valencia
ZIP/Postal Code
46016
Country
Spain
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35440464
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs