Etude : ORIENT-15 / CIBI308A301

ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.

Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : ORIENT-15 / CIBI308A301

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Chimiothérapie / Immunothérapie

Cadre réglementaire : RIPH1

Dernière MÀJ : 30/11/2021
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase III, en double aveugle, visant à évaluer l’efficacité et la sécurité du sintilimab vs placebo, associé à une chimiothérapie, dans le traitement de 1ère ligne du carcinome épidermoïde de l’œsophage métastatique, récidivant ou localement avancé non résécable

Spécialité : Organes digestifs
Localisation : C15 - Tumeur maligne de l'oesophage
Informations complémentaires
Schéma : STUDY ARMS:
- Experimental: Sintilimab in combination with investigator's choice of chemotherapy
TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil

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

- To compare the overall survival (OS) 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);
- 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.

- To compare the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and duration of response (DoR) between two treatment arms in overall population;
- To compare the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and duration of response (DoR) between two treatment arms in subjects with PD-L1 positive ESCC.
- To compare the safety between the two treatment arms.

Phase : III

Stade : Localement avancé à Métastatique

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic ESCC (excluding mixed adenosquamous carcinoma and other histological subtypes).
2. Aged ≥ 18.
3. ECOG PS of 0 or 1.
4. 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 recurrencne must be > 6 months.
5. Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results.
6. Have at least one measurable lesion as per RECIST v1.1.
7. Adequate organs and bone marrow functions, as defined below:
1) Complete blood count: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet (PLT) count ≥ 100 × 109/L, hemoglobin (HGB) ≥ 9.0 g/dL. Note: Subjects cannot receive blood transfusion, erythropoietin (EPO), or Granulocyte-colony stimulating factor (GSF) within 7 days prior to the blood collection.
2) Hepatic function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN in subjects without hepatic metastasis; TBIL ≤ 1.5 × ULN, ALT and AST ≤ 5 × ULN in subjects with hepatic metastasis.
3) Renal function: urine protein < 2+ from random sample or < 1 g from 24-hour urine collection, and creatinine clearance rate (Ccr) ≥ 60 mL/min by Cockcroft-Gault formula.
The calculations of Ccr for one subject must use the same formula throughout the entire study.
4) Adequate coagulation function, defined as international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN; if the subject is receiving anticoagulant therapy, the results of coagulation tests need to be within the acceptable range for anticoagulants.
Expected survival ≥ 12 weeks.
9. Subject (female subjects of childbearing age or male subjects whose partners are of childbearing age) must take effective contraceptive measures during the entire course of the trial and until 180 days after the last dose.
10. Signed the informed consent form (ICF) and be able to comply with the scheduled follow-up visits and related procedures required in the protocol.

Critères de non-inclusion : 1. ESCC with endoscopy-confirmed near-complete obstruction requiring interventional therapy.
2. Post stent implantation in the esophagus or trachea with risks of perforation.
3. Received systemic treatment for advanced or metastatic ESCC.
4. Received a Cumulative dose of cisplatin > 300 mg/m2within 12 months to randomization.
5. High risk of hemorrhage or perforations due to tumor invasion in adjacent organs (aorta or trachea), or have fistula formation.
6. Load of hepatic metastasis > 50% of the total liver volume.
7. Received treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug that specifically targets T-cell co-stimulation or immune checkpoint pathways.
8. Enrolled in another interventional clinical study, unless only involved in an observational study (non-interventional) or in the follow-up phase of an interventional study.
9. Received palliative therapy for local lesion within 2 weeks prior to the first dose.
10. 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.
11Received 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.
12. Received a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or be scheduled to receive live attenuated vaccine during the study period.
Note: Seasonal inactivated influenza virus vaccines within 4 weeks prior to the first dose of study treatment are permitted, but attenuated influenza vaccines are not.
13. Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or is scheduled to receive major surgery during the course of the trial.
14. Any toxicity (excluding alopecia, events that are not clinically significant, or asymptomatic laboratory abnormalities) due to prior anti-tumor therapy that has not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 grade 0 or 1 prior to the first dose of study treatment.
15. Known symptomatic central nervous system (CNS) metastasis or carcinomatous meningitis.
16Clinically significant ascites, including ascites that could be detected on physical examination, has been treated with a prior procedure, or currently requires treatment. Asymptomatic subjects with a small amount of ascitic fluid demonstrated by imaging can be enrolled.
17. Moderate bilateral pleural effusion or large unilateral pleural effusion, or effusion resulting in respiratory dysfunction and requiring drainage.
18. Subjects with bone metastases at risk of paraplegia.
19. Known active autoimmune disease requiring treatment or previous disease history within 2 years (subjects with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment, hypothyroidism only requiring thyroid replacement, or type I diabetes only requiring insulin can be enrolled).
20. Known history of primary immunodeficiency diseases.
21. Known active pulmonary tuberculosis.
Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
23. Known allergy to any monoclonal antibody or any formulation or excipient of chemotherapy agents (e.g. paclitaxel, fluorouracil, or cisplatin) in that the subjects is inappropriate to receive TP or CF regimen.
24. HIV-infected subjects (positive anti-HIV antibody).
25. Active or poorly controlled serious infections.
26. Symptomatic congestive heart failure (NYHA Class II–IV) or symptomatic or poorly controlled arrhythmia.
27. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) despite of standard treatment.
28. Any arterial thromboembolic event within 6 months prior to enrollment, including myocardial infarction, unstable angina, cerebrovascular accident, or transient cerebral ischemic attack.
29. Significant malnutrition, such as those requiring continuous parenteral nutrition ≥7 days; excluding those having received intravenous treatment for malnutrition for more than 4 weeks before the first dose of study treatment.
30. History of deep venous thrombosis, pulmonary embolism, or other serious thromboembolic events within 3 months prior to enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis are not considered as "serious" thromboembolisms).

--- For a complete overview of the exclusion criteria refer to the protocol ---
Informations relatives au promoteur
Promoteur :
Innovent Biologics (Suzhou) Co. Ltd.
Type de sponsor : Industriel
China - test

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN
Apicrypt :

Investigateur :
Marie-Pierre GALAIS

Corentin LE GALLIC

Statut de l'essai : OUVERT

MAJ : 09/02/2021