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

Esophageal Squamous Cell Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03748134
• Other study ID #: CIBI308A301
• Secondary ID: 2020-000533-40
• Status: Completed
• Phase: Phase 3
• Start date: December 24, 2018
• Est. completion date: July 29, 2023

Study information

• Verified date: October 2023
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 746
• Est. completion date: July 29, 2023
• Est. primary completion date: September 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

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

Drug:
• Cisplatin
75mg/m^2 IV Q3W day 1
• 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
• Fluorouracil
800 mg/m^2 IV continuous infusion over 24 hours daily on Days 1-5 Q3W
• Placebo
For weight <60kg, 3mg/kg IV Q3W day 1, and for weight=60kg, 200mg IV Q3W day 1

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.	Fortrea

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  China,  France,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	From date of randomization until the date of death from any cause, assessed up to 40 months.
Primary	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	From date of randomization until the date of death from any cause, assessed up to 40 months.
Secondary	ORR in overall population	To compare the objective response rate between the two treatment arms in ITT population	From date of randomization up to 28 months.
Secondary	PFS in overall populationsubjects in ITT population	To compare the progression-free survival between the two treatment arms in ITT population	From date of randomization up to 28 months
Secondary	DCR in overall population	To compare the disease control rate between the two treatment arms in ITT population	From date of randomization up to 28 months
Secondary	DoR in overall population	To compare the duration of response between the two treatment arms in ITT population	From date of randomization up to 28 months
Secondary	ORR - PD-L1 positive	To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population	From date of randomization up to 28 months
Secondary	DCR - PD-L1 positive	To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population	From date of randomization up to 28 months
Secondary	DoR - PD-L1 positive	To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population	From date of randomization up to 28 months
Secondary	PFS - PD-L1 positive	To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population	From date of randomization up to 28 months