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This is a study to evaluate the efficacy and safety of preoperative treatment with durvalumab combined with neoajuvant therapy (carboplatin, paclitaxel with/without radiation) in locally advanced resectable oesophageal squamous carcinoma.
The primary objective of the study is to assess the tumor response (by irRECIST) and pathological response of preoperative treatment with durvalumab combined with neoadjuvant therapy (carboplatin, paclitaxel with/without radiation).
Secondary objectives are:
To assess completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment.
To assess toxicities of durvalumab in combination with chemoradiation. [Time Frame: up to 1 year] To assess completion of chemotherapy with/without radiation treatment. To assess withdrawal rate from surgery. To assess delay rate from surgery. To assess R0 resection rate. To assess post-operative complications. Progression Free Survival. [ Time Frame: up to 24 months ] Overall Survival. [ Time Frame: up to 24 months ]
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| durvalumab and neoadjuvant therapy | Experimental | durvalumab 1500mg i.v. day 1-22-43-64 Carboplatin AUC = 4-5 i.v day 1-22-43-64 Paclitaxel 75 mg/m2 i.v day 1-22-43-64 with/without Radiotherapy 23 x 1.8 Gy |
|
| normal saline and neoadjuvant therapy | Placebo Comparator | normal saline 500ml i.v. day 1-22-43-64 Carboplatin AUC = 4-5 i.v day 1-22-43-64 Paclitaxel 75 mg/m2 i.v day 1-22-43-64 with/without Radiotherapy 23 x 1.8 Gy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Durvalumab | Drug | Durvalumab 1500mg i.v. day 1-22-43-64 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| tumor response | assess the tumor response (by irRECIST) of preoperative treatment with durvalumab combined with neoadjuvant therapy | up to 12 months |
| pathological response | assess the pathological response (by CAP classification) of preoperative treatment with durvalumab combined with neoadjuvant therapy | up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment | Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment | up to 3 months |
| Incidence and severity of toxicity |
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Inclusion Criteria:
neutrophiles ≥ 1.5 x 109/L platelets ≥ 100 x 109/L alanine transaminase≤2 x upper normal limit hemoglobin ≥ 5.6 mmol total bilirubin ≤ 1.5 x upper normal limit creatinine clearance (Cockroft) ≥60 ml/min
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jia He, MD | Peking Union Medical College Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Beijing | Beijing Municipality | 100730 | China |
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| ID | Term |
|---|---|
| D000077277 | Esophageal Squamous Cell Carcinoma |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000613593 | durvalumab |
| D016190 | Carboplatin |
| D004358 | Drug Therapy |
| D017239 | Paclitaxel |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D013812 | Therapeutics |
| D043823 | Taxoids |
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| Carboplatin |
| Drug |
Chemotherapy |
|
|
| Paclitaxel | Drug | Chemotherapy |
|
|
| Radiotherapy 23 x 1.8 Gy | Radiation | Radiotherapy 23 x 1.8 Gy |
|
|
Incidence and severity of toxicity defined to CTCAE v4.03 and Radiation Oncology Group (RTOG) criteria |
| up to 12 months |
| Percentage completion of chemotherapy with/without radiation treatment | Percentage completion of chemotherapy with/without radiation treatment | up to 3 months |
| Percentage withdrawal rate from surgery due to durvalumab related complications | Percentage withdrawal rate from surgery due to durvalumab related complications | up to 3 months |
| Percentage delay of surgery due to durvalumab related complications | Percentage delay of surgery due to durvalumab related complications | up to 3 months |
| R0 resection rate | R0 resection rate | up to 3 months |
| Incidence and severity of post-operative complications to the Dindo classification | Incidence and severity of post-operative complications to the Dindo classification | up to 3 months |
| Progression free survival | Progression free survival | up to 24 months |
| Overall survival | Overall survival | up to 24 months |
| D009369 | Neoplasms |
| D018307 | Neoplasms, Squamous Cell |
| D004938 | Esophageal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D043822 |
| Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |