Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
This is a randomized, controlled, multi-center phase II/III study. All patients are resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of perioperative Cadonilimab combined with neoadjuvant chemotherapy versus neoadjuvant chemotherapy in patients with resectable ESCC.
Interventions
Specified doses on specified days.
DRUGCisplatin
IV infusion; 75mg/m2
DRUGPaclitaxel
IV infusion; 175mg/m2
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures). * ≥18 years old and ≤ 75 years (regardless of sex). * Pathologically confirmed esophageal squamous cell carcinoma, assessed as resectable. * Adequate pulmonary function. * Adequate tumor tissue samples. * ECOG performance status of 0-1. * Adequate organ function. * Within 7 days prior to the first dose, women of childbearing potential must have a negative urine or serum pregnancy test and agree to use effective contraception during the study treatment period and for 120 days after the last dose.
Exclusion criteria
* Presence of suspected distant metastatic lesions, or locally advanced unresectable disease. * Histologically confirmed as other pathological types. * Previous surgery precludes the use of gastric substitution for esophageal reconstruction in the current procedure. * History of other malignant tumors within the past 5 years. * Within 4 weeks prior to randomization, presence of conditions such as severe esophagogastric varices, active ulcers, unhealed wounds, gastrointestinal perforation, or intestinal obstruction. * Active or documented history of inflammatory bowel disease. * Clinically symptomatic or recurrent pleural, pericardial, or ascitic fluid requiring drainage. * Uncontrolled concurrent illnesses. * Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to randomization. * History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment. * History of severe bleeding tendency or coagulation dysfunction. * Arterial thromboembolic events within 6 months prior to randomization. * History or current presence of non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoids. * Known psychiatric disorders, drug abuse, or substance addiction. * Pregnant or lactating women. * Prior systemic or local antitumor therapy for locally advanced esophageal squamous cell carcinoma. * Systemic non-specific immunomodulatory therapy within 2 weeks prior to randomization. * Major surgery or severe trauma within 4 weeks prior to randomization. * Known allergy to any component of the investigational drug(s). * Active autoimmune disease requiring systemic treatment within 2 years prior to randomization. * Active hepatitis B infection. * Known active tuberculosis. * Severe infections within 4 weeks prior to randomization. * History of immunodeficiency or positive HIV test. * Known active syphilis infection. * Live vaccination within 4 weeks prior to randomization or planned during the study. * History of allogeneic organ transplantation or hematopoietic stem cell transplantation. * Is currently participating in a study of an investigational agent or using an investigational device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) rate as assessed by the investigator | Up to approximately 2 years | Proportion of subjects with no tumor residue in the primary tumor and regional lymph nodes. |
| Adverse Event (Phase II stage) | Up to approximately 5 years | Incidence and severity of adverse events (AEs), rate of delayed surgery, and clinically significant abnormal laboratory findings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival (EFS) | Up to approximately 5 years | Time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. |
| Disease Free Survival (DFS) | Up to approximately 5 years | Time from surgery to local or distant recurrence, or death due to any cause. |
| Overall Survival (OS) | Up to approximately 5 years | Time from randomization until death from any cause. |
| Major Pathological Response (MPR) rate as assessed by the investigator | Up to approximately 2 years | Proportion of subjects with ≤10% residual live tumor cells as assessed by the investigator. |
| Disease Control Rate (DCR) | Up to approximately 2 years | Evaluation of DCR based on RECIST v1.1 |
| Pharmacokinetics (PK) | Up to approximately 2 years | PK parameters: serum concentrations of Cadonilimab at different point of time |
| Anti-Drug Antibodies(ADAs) | Up to approximately 2 years | Proportion of subjects with detectable ADA. |
| Overall Response Rate (ORR) | Up to approximately 2 years | Proportion of subjects with complete response (CR) or partial response (PR) during the neoadjuvant stage. |
| R0 resection rate | Up to approximately 2 years | Proportion of subjects with pathologically complete resection of primary tumors |
Countries
China
Contacts
Primary ContactWenting Li
Outcome results
None listed