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Esophageal Squamous Cell CarcinomaPhase 3NCT03748134

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

A Phase 3 study testing Sintilimab, Cisplatin and Paclitaxel in people with Esophageal Squamous Cell Carcinoma, run by Innovent Biologics (Suzhou) Co. Ltd. at 48 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Esophageal Squamous Cell Carcinoma
What is being tested?
Sintilimab, Cisplatin and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
746 participants
Where
48 sitesin 7 countries
Study dates
24 Dec 2018to 29 Jul 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

48 sites in 7 countries.

48 sites in 7 countries

Spain15 sites

  • Hospital del Mar

    Barcelona, 08001

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario de Fuenlabrada

    Fuenlabrada, 28942

  • Hospital Universitari de Girona Doctor Josep Trueta

    Girona

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida, 25198

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 280402

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Clínica Universidad de Navarra

    Pamplona, 31008

  • Parc Taulí Sabadell Hospital Universitari

    Sabadell, 08208

  • University Hospital Marqués de Valdecilla

    Santander, Cantabria, 39008

  • Complexo Hospitalario Universitario de Santiago

    Santiago de Compostela, 15706

  • Hospital Universitario Virgen Macarena

    Seville, 41003

  • Consorci Hospital General Universitari de València

    Valencia, 46016

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

France13 sites

  • Hôpital Jean Minjoz

    Bettancourt-la-Ferrée, 25000

  • Institut Bergonié

    Bordeaux, 33000

  • Centre François Baclesse

    Caen, 14000

  • CHU Estaing

    Clermont-Ferrand, 63000

  • CHU Estaing

    Clermont-Ferrand, 63100

  • Faculte de Medecine

    Dijon, 21000

  • Universite de Bourgogne - Faculte de Medecine - INSERM U866

    Dijon, 21079

  • Oscar Lambret Centre

    Lille, 59020

  • CHU Hôpital de la Timone

    Marseille, 13005

  • Hôpital Européen Georges Pompidou

    Paris, 75015

  • CHU de Poitiers

    Poitiers, 86021

  • Hôpital Charles-Nicolle de Rouen

    Rouen, 76000

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy, 54500

Other trials in France

United States7 sites

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

    Anaheim, California, 92835

  • Texas Oncology, P.A.

    Austin, Texas, 78705

  • IACT Health - John B. Amos Cancer center

    Columbus, Georgia, 31904

  • Rocky Mountain Cancer Centers, LLP

    Denver, Colorado, 80218

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine

    Orange, California, 92868

  • Northwest Cancer Specialists, P.C.

    Vancouver, Washington, 98684

Other trials in United States

Australia5 sites

  • Border Medical Oncology

    East Albury, New South Wales, 2640

  • Austin Hospital

    Heidelberg, Victoria, 3079

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • St John of God Subiaco Hospital

    Subiaco, Western Australia, 6008

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

Belgium5 sites

  • Cliniques Universitaires Saint-Luc Av.

    Brussels, Hippocrate 10, 1200

  • Institut Jules Bordet

    Brussels, 1000

  • University Hospital Gent

    Ghent, Corneel Heymanslaan 10, 9000

  • Universitair Ziekenhuis Leuven

    Leuven, Herestraat 49, 3000

  • Centre Hospitalier Regional de Verviers

    Verviers, 4800

Other trials in Belgium

Hungary2 sites

  • Országos Onkológiai Intézet

    Budapest, Ráth György U. 7-9, 1122

  • Jósa András Oktatókórház

    Nyíregyháza, Szent István U. 68, 4400

Other trials in Hungary

China1 site

  • Beijing Cancer Hospital

    Beijing

Other trials in China

About this study

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)

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

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
Medical subject headings
Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Neoplasms, Squamous Cell, Esophageal Diseases, Carcinoma, Squamous Cell, Gastrointestinal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SintilimabBiological

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

  • CisplatinDrug

    75mg/m^2 IV Q3W day 1

  • PaclitaxelDrug

    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

  • FluorouracilDrug

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

  • PlaceboDrug

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

Study groups in NCT03748134
Study groupRoleWhat they receive
Randomized Part: Experimental: Sintilimab + chemotherapyExperimentalSintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
Receives: Biological: Sintilimab; Drug: Cisplatin; Drug: Paclitaxel; Drug: Fluorouracil
Randomised Part: Active Comparator: Placebo + chemotherapyActive comparatorPlacebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
Receives: Drug: Cisplatin; Drug: Paclitaxel; Drug: Fluorouracil; Drug: Placebo
Open-label part: Sintilimab+ chemotherapyExperimentalSintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
Receives: Biological: Sintilimab; Drug: Cisplatin; Drug: Paclitaxel; Drug: Fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: From date of randomization until the date of death from any cause, assessed up to 40 months.

  2. 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

    Measured: From date of randomization until the date of death from any cause, assessed up to 40 months.

Secondary outcomes (8)

  1. ORR in overall population

    To compare the objective response rate between the two treatment arms in ITT population

    Measured: From date of randomization up to 28 months.

  2. PFS in overall populationsubjects in ITT population

    To compare the progression-free survival between the two treatment arms in ITT population

    Measured: From date of randomization up to 28 months

  3. DCR in overall population

    To compare the disease control rate between the two treatment arms in ITT population

    Measured: From date of randomization up to 28 months

  4. DoR in overall population

    To compare the duration of response between the two treatment arms in ITT population

    Measured: From date of randomization up to 28 months

  5. ORR - PD-L1 positive

    To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population

    Measured: From date of randomization up to 28 months

  6. DCR - PD-L1 positive

    To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population

    Measured: From date of randomization up to 28 months

  7. DoR - PD-L1 positive

    To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population

    Measured: From date of randomization up to 28 months

  8. PFS - PD-L1 positive

    To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population

    Measured: From date of randomization up to 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2018
  2. Study start24 Dec 2018
  3. Primary completion9 Sep 2021
  4. Study completion29 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
746 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03748134
Sponsor's protocol ID
CIBI308A301
Other IDs
2020-000533-40
Status last verified
Oct 2023
First submitted
12 Nov 2018
Last updated
24 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38800802

  • 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.

    PubMed 37139963

  • 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.

    PubMed 35440464

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sintilimab, Cisplatin and Paclitaxel in people with Esophageal Squamous Cell Carcinoma, run by Innovent Biologics (Suzhou) Co. Ltd. at 48 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in Spain, France, United States, Australia, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

OS in overall population (time frame: From date of randomization until the date of death from any cause, assessed up to 40 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03748134, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2023.

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