Clinical trial NCT03748134: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Fortrea
First posted: 2018-11-20
Enrollment: 746
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: OS in overall population
timeFrame: From date of randomization until the date of death from any cause, assessed up to 40 months.
measure: OS in PD-L1 positive population
timeFrame: From date of randomization until the date of death from any cause, assessed up to 40 months.
Secondary outcomes:
measure: ORR in overall population
timeFrame: From date of randomization up to 28 months.
measure: PFS in overall populationsubjects in ITT population
timeFrame: From date of randomization up to 28 months
measure: DCR in overall population
timeFrame: From date of randomization up to 28 months
measure: DoR in overall population
timeFrame: From date of randomization up to 28 months
measure: ORR - PD-L1 positive
timeFrame: From date of randomization up to 28 months
measure: DCR - PD-L1 positive
timeFrame: From date of randomization up to 28 months
measure: DoR - PD-L1 positive
timeFrame: From date of randomization up to 28 months
measure: PFS - PD-L1 positive
timeFrame: From date of randomization up to 28 months
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center
state: California
city: Orange
country: United States
facility: UC Irvine
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Columbus
country: United States
facility: IACT Health - John B. Amos Cancer center
state: Georgia
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Austin
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: East Albury
country: Australia
facility: Border Medical Oncology
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Gent
country: Belgium
facility: University Hospital Gent
state: Corneel Heymanslaan 10
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Herestraat 49
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc Av.
state: Hippocrate 10
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Verviers
country: Belgium
facility: Centre Hospitalier Regional de Verviers
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bettancourt La Ferree
country: France
facility: Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Dijon
country: France
facility: Faculte de Medecine
city: Dijon
country: France
facility: Universite de Bourgogne - Faculte de Medecine - INSERM U866
city: Lille
country: France
facility: Oscar Lambret Centre
city: Marseille
country: France
facility: CHU Hôpital de la Timone
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rouen
country: France
facility: Hôpital Charles-Nicolle de Rouen
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
state: Ráth György U. 7-9
city: Nyíregyháza
country: Hungary
facility: Jósa András Oktatókórház
state: Szent István U. 68
city: Santander
country: Spain
facility: University Hospital Marqués de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Sabadell
country: Spain
facility: Parc Taulí Sabadell Hospital Universitari
city: Santiago De Compostela
country: Spain
facility: Complexo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Consorci Hospital General Universitari de València
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References:
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.