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

NCT ID: NCT03748134

Last Updated: 2023-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

746 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-24

Study Completion Date

2023-07-29

Brief Summary

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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

Detailed Description

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Conditions

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Esophageal Squamous Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Randomized Part: Experimental: Sintilimab + chemotherapy

Sintilimab in combination with investigator's choice of chemotherapy

TP regimen: Cisplatin + paclitaxel

or

CP regimen: Cisplatin + fluorourcil

Group Type EXPERIMENTAL

Sintilimab

Intervention Type BIOLOGICAL

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

Cisplatin

Intervention Type DRUG

75mg/m\^2 IV Q3W day 1

Paclitaxel

Intervention Type 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

Intervention Type DRUG

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

Randomised Part: Active Comparator: Placebo + chemotherapy

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

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

75mg/m\^2 IV Q3W day 1

Paclitaxel

Intervention Type 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

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Open-label part: Sintilimab+ chemotherapy

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

Group Type EXPERIMENTAL

Sintilimab

Intervention Type BIOLOGICAL

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

Cisplatin

Intervention Type DRUG

75mg/m\^2 IV Q3W day 1

Paclitaxel

Intervention Type 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

Intervention Type DRUG

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

Interventions

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Sintilimab

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

Intervention Type BIOLOGICAL

Cisplatin

75mg/m\^2 IV Q3W day 1

Intervention Type 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

Intervention Type DRUG

Fluorouracil

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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

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 Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fortrea

INDUSTRY

Sponsor Role collaborator

Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center

Anaheim, California, United States

Site Status

UC Irvine

Orange, California, United States

Site Status

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, United States

Site Status

IACT Health - John B. Amos Cancer center

Columbus, Georgia, United States

Site Status

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Texas Oncology, P.A.

Austin, Texas, United States

Site Status

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States

Site Status

Border Medical Oncology

East Albury, New South Wales, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

St John of God Subiaco Hospital

Subiaco, Western Australia, Australia

Site Status

University Hospital Gent

Ghent, Corneel Heymanslaan 10, Belgium

Site Status

Universitair Ziekenhuis Leuven

Leuven, Herestraat 49, Belgium

Site Status

Cliniques Universitaires Saint-Luc Av.

Brussels, Hippocrate 10, Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

Centre Hospitalier Regional de Verviers

Verviers, , Belgium

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Hôpital Jean Minjoz

Bettancourt-la-Ferrée, , France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

Centre François Baclesse

Caen, , France

Site Status

CHU Estaing

Clermont-Ferrand, , France

Site Status

CHU Estaing

Clermont-Ferrand, , France

Site Status

Faculte de Medecine

Dijon, , France

Site Status

Universite de Bourgogne - Faculte de Medecine - INSERM U866

Dijon, , France

Site Status

Oscar Lambret Centre

Lille, , France

Site Status

CHU Hôpital de la Timone

Marseille, , France

Site Status

Hôpital Européen Georges Pompidou

Paris, , France

Site Status

CHU de Poitiers

Poitiers, , France

Site Status

Hôpital Charles-Nicolle de Rouen

Rouen, , France

Site Status

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status

Országos Onkológiai Intézet

Budapest, Ráth György U. 7-9, Hungary

Site Status

Jósa András Oktatókórház

Nyíregyháza, Szent István U. 68, Hungary

Site Status

University Hospital Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario de Fuenlabrada

Fuenlabrada, , Spain

Site Status

Hospital Universitari de Girona Doctor Josep Trueta

Girona, , Spain

Site Status

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Clínica Universidad de Navarra

Pamplona, , Spain

Site Status

Parc Taulí Sabadell Hospital Universitari

Sabadell, , Spain

Site Status

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Consorci Hospital General Universitari de València

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Countries

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United States Australia Belgium China France Hungary Spain

References

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Lu Z, Kong L, Wang B, Wang J, Liu L, Shu Y, Yang L, Sun G, Cao G, Ji Y, Cui T, Liu H, Qiu W, Li N, Li G, Luo H, Hou X, Zhang Y, Yue W, Xue L, Liu Z, Pan Y, Gao S, Wang X, Pan Z, Zhang S, Lin G, Xie Y, Gu K, Ren T, Li W, Li T, Wang S, He W, Fan Y, Liang J, Xia B, Zhao L, Wang S, Shen L. Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study. EClinicalMedicine. 2024 May 17;72:102623. doi: 10.1016/j.eclinm.2024.102623. eCollection 2024 Jun.

Reference Type DERIVED
PMID: 38800802 (View on PubMed)

Zhang Y, Li C, Du K, Pengkhun N, Huang Z, Gong M, Li Y, Liu X, Li L, Wang D, Wang C, Chen F, Li J. Comparative analysis of immune checkpoint inhibitors in first-line treatment of esophageal squamous cell carcinoma: a network meta-analysis. Immunotherapy. 2023 Jul;15(10):737-750. doi: 10.2217/imt-2022-0236. Epub 2023 May 4.

Reference Type DERIVED
PMID: 37139963 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35440464 (View on PubMed)

Other Identifiers

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2020-000533-40

Identifier Type: REGISTRY

Identifier Source: secondary_id

CIBI308A301

Identifier Type: -

Identifier Source: org_study_id

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