Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma ( ORIENT-15 )
- Conditions
- Esophageal Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT03748134
- Lead Sponsor
- Innovent Biologics (Suzhou) Co. Ltd.
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 746
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Randomized Part: Experimental: Sintilimab + chemotherapy Sintilimab Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomized Part: Experimental: Sintilimab + chemotherapy Cisplatin Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomized Part: Experimental: Sintilimab + chemotherapy Paclitaxel Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomised Part: Active Comparator: Placebo + chemotherapy Cisplatin Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomised Part: Active Comparator: Placebo + chemotherapy Paclitaxel Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomised Part: Active Comparator: Placebo + chemotherapy Fluorouracil Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomised Part: Active Comparator: Placebo + chemotherapy Placebo Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Open-label part: Sintilimab+ chemotherapy Sintilimab Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Open-label part: Sintilimab+ chemotherapy Cisplatin Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Open-label part: Sintilimab+ chemotherapy Paclitaxel Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Open-label part: Sintilimab+ chemotherapy Fluorouracil Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil Randomized Part: Experimental: Sintilimab + chemotherapy Fluorouracil Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
- Primary Outcome Measures
Name Time Method OS in overall population From date of randomization until the date of death from any cause, assessed up to 40 months. 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)
OS in PD-L1 positive population From date of randomization until the date of death from any cause, assessed up to 40 months. 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
- Secondary Outcome Measures
Name Time Method ORR in overall population From date of randomization up to 28 months. To compare the objective response rate between the two treatment arms in ITT population
PFS in overall populationsubjects in ITT population From date of randomization up to 28 months To compare the progression-free survival between the two treatment arms in ITT population
DCR in overall population From date of randomization up to 28 months To compare the disease control rate between the two treatment arms in ITT population
DoR in overall population From date of randomization up to 28 months To compare the duration of response between the two treatment arms in ITT population
ORR - PD-L1 positive From date of randomization up to 28 months To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population
DCR - PD-L1 positive From date of randomization up to 28 months To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population
DoR - PD-L1 positive From date of randomization up to 28 months To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population
PFS - PD-L1 positive From date of randomization up to 28 months To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population
Trial Locations
- Locations (47)
St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center
🇺🇸Anaheim, California, United States
UC Irvine
🇺🇸Orange, California, United States
Rocky Mountain Cancer Centers, LLP
🇺🇸Denver, Colorado, United States
IACT Health - John B. Amos Cancer center
🇺🇸Columbus, Georgia, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Texas Oncology, P.A.
🇺🇸Austin, Texas, United States
Northwest Cancer Specialists, P.C.
🇺🇸Vancouver, Washington, United States
Border Medical Oncology
🇦🇺East Albury, New South Wales, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Scroll for more (37 remaining)St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center🇺🇸Anaheim, California, United States